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BIOMARKER:

IKZF1 deletion

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Other names: IKZF1, IKAROS Family Zinc Finger 1, Zinc Finger Protein Subfamily 1A 1 (Ikaros), Protein Phosphatase 1 Regulatory Subunit 92, Ikaros Family Zinc Finger Protein 1, Lymphoid Transcription Factor LyF-1, DNA-Binding Protein Ikaros, ZNFN1A1, IKAROS, LYF1, IK1, IKAROS Family Zinc Finger 1 (Ikaros), CLL-Associated Antigen KW-6, Hs.54452, PPP1R92, PRO0758, CVID13, LyF-1
Entrez ID:
Related biomarkers:
15d
Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity. (PubMed, Br J Haematol)
Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.
Journal • Minimal residual disease
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5)
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CDKN2A deletion • IKZF1 deletion
1m
Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach. (PubMed, Front Mol Biosci)
High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.
Journal
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JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • P2RY8 (P2Y Receptor Family Member 8)
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IKZF1 deletion • CRLF2 overexpression
2ms
IKZF1 Alterations and Therapeutic Targeting in B-Cell Acute Lymphoblastic Leukemia. (PubMed, Biomedicines)
IKZF1 deletions are associated with treatment resistance and inferior outcomes. Early identification of IKZF1 deletions in B-ALL may inform the intensification of therapy and other potential treatment strategies to improve outcomes in this high-risk leukemia.
Review • Journal
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
3ms
Association of CDKN2A/2B deletion with relapse after hematopoietic stem cell transplantation for acute lymphoblastic leukemia. (PubMed, Blood Cell Ther)
Although they were positive for pre-transplant MRD, no relapse was observed in patients with wild-type copy number variations in IKZF1 or CDKN2A/2B. CDKN2A/2B copy number variation is a crucial factor that can be confirmed at initial onset as a post-transplant prognostic factor of Ph+ALL.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5)
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CDKN2A deletion • IKZF1 deletion
4ms
Suppressing IKZF1 Deletion-Mediated Activation of Ras Oncogenic Signaling By the Combination of Azacitidine and Flumatinib in High-Risk B-ALL (ASH 2023)
Moreover, about 80% of Ph +B-ALL patients have the IKZF1 deletion, our ChIP-seq data showed that IKZF1-encoded Ikaros protein binds to the promoter region of PTPN11 and CK2 inhibitor CX4945 as Ikaros function activator dramatically increase the Ikaros binding to the promoter of PTPN11 in B-ALL cells and Ikaros directly suppresses its promoter activity (Fig. Conclusions The combination of AZA and FLU has a synergistic anti-leukemia effect on cell proliferation arrest and apoptosis in Ph +ALL cells with IKZF1-deletion by targeting Ikaros/PTPN11/Ras oncogenic signaling. Our data provide experimental evidence for a new potential combination of AZA with FLU in the therapy of Ph +ALL and highlight the likelihood of the novel combination in ALL patients.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)
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IKZF1 deletion
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azacitidine • Hansoh Xinfu (flumatinib) • silmitasertib (CX-4945)
4ms
Transcriptome Sequencing Allows Comprehensive Genomic Characterization of Pediatric B-Lymphoblastic Leukemia (B-ALL) in an Academic Clinical Laboratory. (PubMed, J Mol Diagn)
RNA-Seq analysis also detected large copy number abnormalities, oncogenic hot-spot sequence variants, and intragenic IKZF1 deletions. Our pilot study confirms the feasibility of implementing an RNA-Seq workflow for clinical diagnosis of molecular subtypes in pediatric B-ALL, reinforcing that RNA-Seq represents a promising global genomic assay for this heterogeneous leukemia.
Journal
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RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • IKZF1 (IKAROS Family Zinc Finger 1) • PAX5 (Paired Box 5) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • NUTM1 (NUT Midline Carcinoma Family Member 1) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2) • DUX4 (Double Homeobox 4) • ZNF384 (Zinc Finger Protein 384)
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IKZF1 deletion
5ms
Adverse Prognostic Role of Copy Number Alterations and Mutations in Adults with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ASH 2023)
Our data showed that IKZF1 or CDKN2A/B deletions and TP53 mutations may confer a poor prognosis for adult Ph-negative B-cell precursor ALL in the setting of intensive chemotherapy and allo-HCT. The combination of genomic abnormalities and minimal residual disease response may further refine risk stratification and better select patients who could benefit from novel therapeutic approaches.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • JAK2 (Janus kinase 2) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5) • EBF1 (EBF Transcription Factor 1)
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TP53 mutation • CDKN2A deletion • IKZF1 deletion
5ms
Exploring the Heterogeneity of Response to Blinatumomab in High-Risk Philadelphia-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: An Analysis from the QUEST Sub-Study of the Graall-2014/B Trial (ASH 2023)
Among them, younger patients (<45y), patients with WBC<30 G/L, with poor prednisone response, with IKZF1 deletion or with Ph-like disease had a significantly higher chance to be MRD3-negative after BLIN than after chemotherapy. In adult patients with Ph-negative BCP-ALL who experience an overall benefit of BLIN in consolidation, the present study reveals a heterogeneous landscape of response among genetic entities. Larger prospective studies should further explore this heterogeneity to refine implementation of BLIN in frontline setting.
KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • DUX4 (Double Homeobox 4) • ZNF384 (Zinc Finger Protein 384)
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KMT2A rearrangement • MLL rearrangement • IKZF1 deletion
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Blincyto (blinatumomab) • prednisone
5ms
Crebbp Mutations Are Associated with Slow Minimal Residual Response to Upfront Induction Chemotherapy in Pediatric High-Hyperdiploid B-Cell Precursor Acute Lymphoblastic Leukemia Treated in the AIEOP-BFM ALL 2009 Protocol (ASH 2023)
Therefore, the inclusion of CREBBP mutated patients in very low risk protocols should be carefully evaluated. The validation of these findings is ongoing through the analysis of patients treated by other international study groups adopting different chemotherapy backbones.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • CREBBP (CREB binding protein) • AFF1 (AF4/FMR2 Family Member 1)
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KRAS mutation • BRAF mutation • NRAS mutation • NF1 mutation • RAS mutation • CREBBP mutation • IKZF1 deletion • IKZF1 mutation
5ms
LONG-TERM Results of the Frontline Dasatinib/Blinatumomabprotocol (D-ALBA, GIMEMA LAL2116) for Adult Ph+ Acutelymphoblastic Leukemia (ASH 2023)
These results pave the way for a new era in the treatment of adult Ph+ ALL patients. Vignetti et al, Blood 2007 Foà et al, Blood 2011 Chiaretti et al, Haematologica 2016 Chiaretti et al, Haematologica 2021 Martinelli et al, Blood Advances 2022 Foà et al, N Engl J Med 2020 Foà & Chiaretti, N Engl J Med 2022
Clinical • IO biomarker
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ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
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ABL1 T315I • IKZF1 deletion
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dasatinib • Blincyto (blinatumomab)
5ms
Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)
1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.
Clinical
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ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
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DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation
5ms
Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023)
With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were very rare in this pt population, supporting their role in CML disease progression. The high frequency of co-occurrence of BCR::ABL1 mutations and blood cancer gene mutations in CML-CP is an important finding since cancer gene mutations could modify response to TKIs in individual pts.
Clinical • Clinical data
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ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • IKZF1 (IKAROS Family Zinc Finger 1)
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BCR-ABL1 T315I • RUNX1 mutation • ASXL1 mutation • MET mutation • ABL1 T315I • IKZF1 deletion • IKZF1 mutation • ABL1 deletion
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Bosulif (bosutinib) • Scemblix (asciminib) • denifanstat (TVB-2640)
5ms
Allo-HSCT Improved Outcome of High Risk ALL in Pediatric-Inspired PDT-ALL-2016 Cohort (ASH 2023)
Seftel et.al, AJH, 2015) that counterbalanced the benefit of CIR by allo-HSCT, which highlight the importance of experienced management for total therapy in adult ALL. This research was supported by the National Natural Science Foundation of China(NFSC82170163, 81970147), Clinical Study of Nanfang Hospital(LC2016ZD009/2019CR012).
Clinical
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
5ms
Mutually-Exclusive Pathways between IKZF1plus and RAS Mutations and TP53 double-Hit Alterations Lead Relapse in B-Other, Ph-like and Hyperdiploidy Genetic Groups in Adult B-Cell Acute Lymphoblastic Leukemia (ASH 2023)
Eighty-six percent (6/7) of Ph+ patients who received imatinib treatment presented ABL1 mutations that were detected exclusively at relapse... Our results highlight the clinical importance of the TP53 alterations and the IKZF1plus profile as prognostic factors in adult BCP-ALL, suggesting they might help guiding more personalized therapeutic strategies to improve outcomes in this group of BCP-ALL patients. Grants: SACYL(GRS2386/A/21,GRS2385/A/21,GRS2527/A/22,GRS2506/A/22), JCyL SA118P20, FMM21/002 AP176752021, Pfizer 69383919.
Clinical • IO biomarker
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TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
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TP53 mutation • RAS mutation • CDKN2A deletion • KMT2A rearrangement • MLL rearrangement • IKZF1 deletion
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imatinib
5ms
Cancer Genomic Profiling and Minimal Residual Disease Monitoring By Cell-Free DNA Sequencing in Pediatric Leukemia (ASH 2023)
Our study has demonstrated the utility of cfDNA sequencing to identify both sequence and structural somatic mutations in childhood acute leukemia. This approach will be useful to monitor disease, as well as providing a non-invasive diagnostic approach.
Clinical • Minimal residual disease • Cell-free DNA
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion • KRAS deletion
6ms
Toblerone: detecting exon deletion events in cancer using RNA-seq. (PubMed, F1000Res)
We applied the algorithm, named Toblerone, to a cohort of 99 B-ALL paediatric samples including validated IKZF1 deletions. Furthermore, we developed a graphical desktop app for non-bioinformatics users that can quickly and easily identify and report deletions in IKZF1 from RNA-seq data with informative graphical outputs.
Journal
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
7ms
Exploring the Genetic Landscape of B‑ALL: A Comparative Analysis of Copy Number Alterations in Adult and Pediatric B‑ALL Patients (SOHO 2023)
Our findings indicate an overall higher proportion of >3CNAs (39% vs 16%) in the adult B-ALL patients as well as much higher prevalence of IKZF1 deletions (53.4% vs 16.6%).
Clinical
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • JAK2 (Janus kinase 2) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CD123 (Interleukin 3 Receptor Subunit Alpha) • PAX5 (Paired Box 5) • EBF1 (EBF Transcription Factor 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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IKZF1 deletion
7ms
Clinical and Molecular Features of Pediatric BCP‑ALL With TSLP Receptor (CRLF2) Expression (SOHO 2023)
In patients with CRLF2 expression, other molecular rearrangements should be searched to determine the proper risk group.
Clinical
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ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • NUP214 (Nucleoporin 214) • P2RY8 (P2Y Receptor Family Member 8) • TSLP (Thymic Stromal Lymphopoietin)
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IKZF1 deletion • CRLF2 mutation
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TruSight RNA Pan-Cancer Panel
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Jakafi (ruxolitinib)
7ms
Dominant-negative type of IKZF1 deletion showed a favorable prognosis in adult B-cell acute lymphoblastic leukemia. (PubMed, Ann Hematol)
The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344).
Journal
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ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion • ABL1 deletion
8ms
Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia. (PubMed, Hemasphere)
We detected 3 novel fusion genes (SFMBT2::DGKD, PDS5B::STAG2, and TDRD5::LPCAT2), for which the sequence and expression were validated by long-read and whole transcriptome sequencing, respectively. OGM and WES identified double hits of SVs and SNVs (ETV6, BTG1, STAG2, MANBA, TBL1XR1, NSD2) in the same patient demonstrating the power of the combined approach to define the landscape of genomic alterations in BCP-ALL.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • IKZF1 (IKAROS Family Zinc Finger 1) • PAX5 (Paired Box 5) • STAG2 (Stromal Antigen 2) • CD4 (CD4 Molecule) • DGKD (Diacylglycerol Kinase Delta) • DRD5 (Dopamine Receptor D5) • GPRC5A (G Protein-Coupled Receptor Class C Group 5 Member A) • IKBKB (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Beta) • LPCAT2 (Lysophosphatidylcholine Acyltransferase 2) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • SFMBT2 (Scm Like With Four Mbt Domains 2) • TBL1XR1 (TBL1X Receptor 1)
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IKZF1 deletion
9ms
Prevalence and prognostic significance of IKZF1 deletion in paediatric acute lymphoblastic leukemia: A systematic review and meta-analysis. (PubMed, Ann Hematol)
In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.
Retrospective data • Review • Journal
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ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion • ABL1 deletion
9ms
The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B-cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols. (PubMed, Br J Haematol)
Conversely, patients with both a good CNA and cytogenetic profile had a superior relapse-free (p ≤ 0.001) and overall survival (p ≤ 0.001) in the cohort, across all risk groups. Taken together, our findings highlight the potential of CNA assessment to refine stratification in ALL.
Journal
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
10ms
Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia. (PubMed, Hemasphere)
Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.
Journal
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CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • PAX5 (Paired Box 5) • P2RY8 (P2Y Receptor Family Member 8)
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IKZF1 deletion • CRLF2 overexpression • IKZF1 overexpression • PAX5 fusion
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birinapant (IGM-9427)
10ms
IKZF1 alterations are not associated with outcomes in Philadelphia-positive acute lymphoblastic leukemia patients enrolled in the FBMTG ALL/MRD2008 trial. (PubMed, Eur J Haematol)
We revealed no relationship between IKZF1 status and survival outcomes in Ph+ ALL patients treated with imatinib/dasatinib combination chemotherapy. Further investigations are warranted to clarify the prognostic significance of IKZF1 in adult Ph+ ALL patients.
Clinical • Journal
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
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dasatinib • imatinib
11ms
GENOMIC AND TRANSCRIPTOMIC PROFILING REVEALS NOVEL GENE FUSIONS AND MARKERS OF CLINICAL RESPONSE IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2023)
With novel gene fusions and uncovered associations between the dynamics of MRD decline, TP53 and RUNX1 high burden mutations in this real-world cohort, our dataset provides valuable, clinically relevant insights to the genomic and transcriptomic landscape of children diagnosed with ALL. Pediatric, ALL, Prognosis, Mutation analysis
Clinical
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • PTEN (Phosphatase and tensin homolog) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • WT1 (WT1 Transcription Factor) • NT5C2 (5'-Nucleotidase Cytosolic II) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • CCND3 (Cyclin D3) • PHF6 (PHD Finger Protein 6)
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TP53 mutation • BCR-ABL1 fusion • RUNX1 mutation • IKZF1 deletion • WT1 mutation • NT5C2 mutation • ETV6 mutation • NT5C mutation • PAX5 fusion • ABL1 deletion
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TruSight RNA Pan-Cancer Panel
11ms
IKZF1 ALTERATIONS HAVE A NEGATIVE IMPACT ON EARLY MOLECULAR RESPONSE AND SURVIVAL OF ADULT PATIENTS WITH B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH GMALL 07/2003 PROTOCOL IN CZECHIA (EHA 2023)
Aims: This work of the Czech Leukemia Study Group for Life is focused on 79 adult B-ALL patients treated with GMALL 07/2003 protocol (and with imatinib in Ph+ ALL)... IKZF1 alterations were more frequent in Ph+ ALL. Their detection correlated with shorter OS in both Ph+ and Ph- ALL adults treated with GMALL 07/2003 protocol. Individuals with IKZF plus had the worse outcome.
Clinical
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ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5)
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CDKN2A deletion • IKZF1 deletion • ABL1 deletion
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imatinib
11ms
ALLO-HSCT OR CHEMOTHERAPY FOR B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN THE FIRST COMPLETE REMISSION: IMPACT OF MRD AND IKZF1 (EHA 2023)
Our study shows that early MRD response and IKZF1 deletion, in contrast to conventional B-ALL risk factors, is an excellent tool to identify patients who may benefit from allo-HSCT or chemotherapy regimens in the context of intensified pediatric-like adult ALL therapy.
Clinical
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
11ms
IMPACT OF IKZF1 DELETION IN RELAPSED AND/OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH CD19-CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY (EHA 2023)
IKZF1 deletion is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with B-ALL treated with CD19-CAR-T. Further mechanisms are needed to explore how tumor intrinsic phenotype promote resistance to the antitumor immune response, and could represent targets to potentiate the efficacy of CAR-T therapy. CAR-T, Adult, Acute lymphoblastic leukemia
CAR T-Cell Therapy • IO biomarker
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IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
11ms
The Prognostic Effect of IKZF1 Deletions in ETV6::RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia. (PubMed, Hemasphere)
There was no evidence to suggest that IKZF1 deletions affected outcome in the small number of ETV6::RUNX1 cases in MRD-guided protocols but that they are related to higher MRD values, higher relapse, and lower survival rates in HeH ALL. Future trials are needed to study whether stratifying by MRD is adequate for HeH patients or additional risk stratification is necessary.
Journal
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RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion
11ms
The prognostic value of IKZF1 in B-cell progenitor acute lymphoblastic leukemia: Results from the EORTC 58951 trial. (PubMed, Pediatr Blood Cancer)
In patients with BCP-ALL from the EORTC 58951 trial, the improvement of the prognostic importance of IKZF1 by considering IKZF1 was not statistically significant.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5)
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CDKN2A deletion • IKZF1 deletion
1year
The prognostic significance of CRLF2 expression at diagnosis in adult Ph-negative B-cell precursor acute lymphoblastic leukemia. (PubMed, Leuk Lymphoma)
Furthermore, CRLF2_H/IKZF1del(+) patients had significantly lower CR, RFS, and OS rates and tended to have lower RFS and OS rates than others in the whole cohort and B-other patients, respectively. Therefore, coexistence of CRLF2_H and IKZF1del at diagnosis predicts poor response and outcome in adult Ph-negative BCP-ALL.
Journal
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CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • P2RY8 (P2Y Receptor Family Member 8)
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IKZF1 deletion • P2RY8-CRLF2 fusion
1year
Structural variants detected by optical genome mapping in acute lymphoblastic leukemia patient-derived xenografts models (AACR 2023)
OGM assays were more comprehensive, and novel rare SVs were identified in ALL. Combining the results of gene fusions between different technologies will provide more accurate predictions for ALL classifications. The combination of aberrant SVs may synergize to influence the efficacy of imatinib, which warrants further investigations.
Clinical
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha) • PRKAR2B (Protein Kinase CAMP-Dependent Type II Regulatory Subunit Beta)
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BCR-ABL1 fusion • KMT2A rearrangement • MLL rearrangement • IKZF1 deletion • ABL1 deletion
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imatinib
1year
Classification and genetics of pediatric B-other Acute Lymphoblastic Leukemia by targeted RNA-sequencing. (PubMed, Blood Adv)
All novel ALL subgroups, except for iAMP21, hyper- and hypodiploid cases were identified. Curiously, we observed higher frequencies of girls within B-'rest' ALLs and boys in PAX5-driven cases.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • EPOR (Erythropoietin Receptor) • GATA3 (GATA binding protein 3) • MEF2D (Myocyte Enhancer Factor 2D) • NUTM1 (NUT Midline Carcinoma Family Member 1) • DUX4 (Double Homeobox 4) • ZNF384 (Zinc Finger Protein 384)
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MLL rearrangement • IKZF1 deletion • CRLF2 rearrangement • IGH-CRLF2 fusion
1year
THE IMPACT OF ALLOGENEIC STEM CELL TRANSPLANTATION IN PH-LIKE PATIENTS: A REPORT FROM THE NATIONAL TREATMENT PROTOCOLS GIMEMA 1913 AND GIMEMA 2317 (EBMT 2023)
Ph-like signature defines a distinct very high-risk group of ALL characterized by worse OS and DFS. The benefit gained by an alloHSCT in patients at high risk of relapse was greater for non-Ph-like compared to Ph-like cases, due to a very high risk for relapse during the first 2 years after alloHSCT in Ph-like patients. These findings strengthen the need to detect this subset at diagnosis in order to optimize treatment and to obtain deeper remission – as in the currently ongoing GIMEMA 2922 trial -before transplantation and to evaluate experimental preemptive treatments after transplantation to prevent relapse.
Clinical
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ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
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IKZF1 deletion