News - CRLF2 rearrangement

11ms

Targeting Senescent Stemlike Subpopulations in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia. (PubMed, Blood)

This dormant ALL subpopulation was effectively eradicated by dual pharmacologic inhibition of BCL-2 and JAK/STAT or SRC/ABL pathways, a clinically-relevant therapeutic strategy. Single cell-derived molecular signatures of this senescence and stem/progenitor-like subpopulation further predicted poor clinical outcomes associated with other high-risk genetic subtypes of childhood B-ALL and thus may have broader prognostic applicability beyond Ph-like ALL.

11 months ago

Journal • IO biomarker

ABL1 (ABL proto-oncogene 1) • BCL2 (B-cell CLL/lymphoma 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2)

CRLF2 rearrangement

12ms

Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia. (PubMed, Leukemia)

Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia 'maintenance' relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.

12 months ago

Journal • Stroma

CRLF2 (Cytokine Receptor Like Factor 2) • TSLP (Thymic Stromal Lymphopoietin)

CRLF2 rearrangement

Jakafi (ruxolitinib)

1year

Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia. (PubMed, Res Sq)

Genomic IKZF1 plus with any IKZF1 deletion, IKZF1 deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The type of IKZF1 alteration, together with the subtype, are informative for risk stratification and predict response in patients with B-ALL.

1 year ago

Journal

ABL1 (ABL proto-oncogene 1) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1)

IKZF1 deletion • CRLF2 rearrangement

1year

Improved Outcomes of Adult Patients with Philadelphia-like Acute Lymphoblastic Leukemia (Ph-Like ALL) Treated within an Integrated Leukemia/Transplant Program with Incorporation of Pediatric Inspired Regimens and Early Allogeneic Transplant (ASH 2024)

Blinatumomab was not used during consolidation therapy in the reported patients. Its incorporation in the routine therapy of newly diagnosed patients may increase the proportion of patients receiving AHCT in a MRD negative state and further improve outcomes in this historically poor risk patient population.

1 year ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • CSF1R (Colony stimulating factor 1 receptor)

CRLF2 rearrangement • JAK2 rearrangement

clonoSEQ

Blincyto (blinatumomab)

1year

Enhanced Flow Cytometry and Next Generation Sequencing Assays for Residual B Lymphoblastic Leukemia (B-ALL) Reveal a Subset with Discordant Results Due to Leukemic Changes Post-Therapy (ASH 2024)

NGS detects very low-level (<0.001%) residual clonal sequences in 22% of patients and the clinical significance remains a matter of investigation. These data suggest that MFC and NGS are complementary and provide more powerful insight into the biology and clinical outcome of B-ALL than either assay alone.

1 year ago

IO biomarker • Next-generation sequencing • Discordant

KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • CD73 (5'-Nucleotidase Ecto) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • CD24 (CD24 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • NRP1 (Neuropilin 1) • CD81 (CD81 Molecule)

CRLF2 rearrangement

clonoSEQ

1year

CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy. (PubMed, J Immunother Cancer)

To our knowledge, these are the first cases of LS to be reported in patients with CRLF2 rearranged acute lymphoblastic leukemia. In addition to raising awareness that this genetic mutation may associate with lineage plasticity, our cases illustrate the importance of multi-modal disease surveillance in the diagnosis of LS.

1 year ago

Journal

KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2)

KMT2A rearrangement • MLL rearrangement • CRLF2 rearrangement

1year

Judicious use of precise fluorescence in situ hybridisation panels guided by population prevalence may assist pragmatic detection of clinically targetable Philadelphia chromosome-like acute lymphoblastic leukaemia fusions: a systematic review. (PubMed, Pathology)

In real-world cohorts, it may be clinically useful to prioritise limited early FISH in B-cell ALL (B-ALL) diagnostic algorithms to identify Ph-like abnormalities that respond to locally available kinase inhibitors to promote and prioritise broad access to effective targeted treatment. Additional studies are required to provide adequately powered validations and verifications of targeted Ph-like FISH panels to confirm sensitivity and specificity against side-by-side gold standard methods, and to define optimal local approaches.

1 year ago

Review • Journal

CRLF2 (Cytokine Receptor Like Factor 2)

CRLF2 rearrangement

over1year

An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome-like acute lymphoblastic leukemia. (PubMed, Hemasphere)

Allogeneic hematopoietic stem cell transplantation was associated with improved prognoses in patients within the high-risk subgroup. In conclusion, this study identified a clinically distinct entity that possesses effective prognostic features and provides potential guidance for refining risk stratification in Ph-like ALL.

over 1 year ago

Journal

JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CRKL (CRK Like Proto-Oncogene, Adaptor Protein) • STAT5A (Signal Transducer And Activator Of Transcription 5A)

CRLF2 rearrangement • JAK2 rearrangement

over1year

MOLECULAR PROFILING OF ALL IN PEDIATRIC PATIENTS TREATED AT SOLCA, GUAYAQUIL. EVALUATION OF PROGNOSTIC VALUE. PRELIMINARY REPORT. (EHA 2024)

This is a preliminary report of the results of NGS analysis of a group of pediatric patients that will allow riskstratification and will provide recommendations of diverse therapeutical approaches within the concept ofpersonalized medicine. The 198 genes panel is ample and identified mutations present in a cluster of 8 genes in the entire set of cases(46/46). We will correlate the obtained mutational profile with response to treatment and relapse considering eternalfactors as nutritional status and access to medical services and medication.

over 1 year ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene 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) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • CSF1R (Colony stimulating factor 1 receptor) • FOXP1 (Forkhead Box P1) • CALR (Calreticulin) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • LZTS1 (Leucine Zipper Tumor Suppressor 1) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • PDGFC (Platelet Derived Growth Factor C)

CRLF2 rearrangement • BCL11B mutation

FusionPlex™ Pan-Heme panel

over1year

IKZF1PLUS alterations contribute to outcome disparities in Hispanic/Latino children with B-lymphoblastic leukemia. (PubMed, Pediatr Blood Cancer)

Our study shows enrichment of high-risk genetic variants in H/L B-ALL and raises consideration for novel therapeutic targets.

over 1 year ago

Journal

ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • P2RY8 (P2Y Receptor Family Member 8) • DUX4 (Double Homeobox 4)

CDKN2A deletion • IKZF1 deletion • CRLF2 rearrangement

2years

Outcome Disparities Among Hispanic and Non-Hispanic Patients with Acute Lymphoblastic Leukemia (ASH 2023)

Our study provides important insights into the demographic and clinical characteristics of patients with ALL and highlights notable disparities between non-Hispanic and Hispanic patients. A higher proportion of Hispanic patients lacked any form of health insurance coverage at the time of diagnosis. Interestingly, the incidence of Philadelphia-positive ALL was found to be higher among non-Hispanic patients, whereas other cytogenetic abnormalities were more prevalent among Hispanic patients.

2 years ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)

CRLF2 rearrangement