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    BIOMARKER:

    Chr del(5q)

    14d
    Sustained yet non-curative response to lenalidomide in relapsed angioimmunoblastic T-cell lymphoma with acquired chidamide resistance: a case report with 10-year follow-up, genetic insights and literature review. (PubMed, Front Oncol)
    Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • RHOA (Ras homolog family member A)
    |
    ARID1A mutation • TET2 mutation • KMT2D mutation • Chr del(5q)
    |
    lenalidomide • Epidaza (chidamide)
    19d
    SF3B1 Gene Mutations and Their Significance for Patients with Myelodysplastic Neoplasms (MDS) (ASH 2024)
    Three are still alive and are undergoing azacitidine treatment at 6.5, 8.5, and 21 months after their diagnosis.Identification of splicing factor gene mutations is an important diagnostic tool for the stratification of MDS patients...Other biological factors such as the mutation variant, association with complex karyotypes, and mutations in other genes, may also affect the prognosis of patients with mutated SF3B1. Therefore, a comprehensive view that includes all cytogenomic, molecular, and clinical data is important for accurate diagnosis and personalized treatment of MDS patients.Supported by MH CZ-DRO 0064165
    Clinical
    |
    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • BCORL1 (BCL6 Corepressor Like 1)
    |
    TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • Chr del(5q) • SF3B1 K666N • SF3B1 K700E
    |
    Archer® VariantPlex® Myeloid panel
    |
    azacitidine
    19d
    Evaluation of the Prognostic Impact of STAG2 in the Molecular International Prognostic Scoring System for Myelodysplastic Syndromes (ASH 2024)
    These variants would meet the required criteria in the IPSS-M to move from a residual value gene to a main effect gene, regarding progression to AML. These results should be confirmed in future multicentric studies.
    STAG2 (Stromal Antigen 2) • PHF6 (PHD Finger Protein 6)
    |
    Chr del(5q)
    |
    OncoKitDx
    2ms
    5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies (clinicaltrials.gov)
    P1, N=20, Recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD14 (CD14 Molecule) • DCK (Deoxycytidine Kinase 2) • DNMT1 (DNA methyltransferase 1) • ITGAM (Integrin, alpha M) • NT5C (5', 3'-Nucleotidase, Cytosolic)
    |
    Chr del(5q)
    |
    azacitidine • decitabine
    3ms
    Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes. (PubMed, Lancet Haematol)
    After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting.
    Review • Journal
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    TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1)
    |
    TP53 mutation • RUNX1 mutation • Chr del(5q) • Chr del(7q)
    8ms
    Myelodysplastic Neoplasms (MDS): The Current and Future Treatment Landscape. (PubMed, Curr Oncol)
    Novel treatments aimed at rational molecular and cellular pathway targets have yielded a number of candidate drugs over recent years; however few new approvals have been granted. With ongoing research, we hope to increasingly offer our MDS patients tailored therapeutic approaches, ultimately decreasing morbidity and mortality.
    Review • Journal
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    TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
    |
    SF3B1 mutation • Chr del(5q)
    9ms
    Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation
    |
    cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
    9ms
    Diagnostic challenges and proposed classification of myeloid neoplasms with overlapping features of thrombocytosis, ring sideroblasts and concurrent del(5q) and SF3B1 mutations. (PubMed, Haematologica)
    Not available.
    Journal
    |
    SF3B1 (Splicing Factor 3b Subunit 1)
    |
    SF3B1 mutation • Chr del(5q)
    9ms
    HSPA9/mortalin inhibition disrupts erythroid maturation through a TP53-dependent mechanism in human CD34+ hematopoietic progenitor cells. (PubMed, Cell Stress Chaperones)
    We showed that inhibition of HSPA9 disrupts erythroid maturation in human CD34+ hematopoietic progenitor cells, through a TP53-dependent mechanism. Our findings not only indicate that reduced levels of HSPA9 may contribute to anemia observed in del(5q)-associated MDS patients, but also provide new insights into potential mechanisms of anemia.
    Journal
    |
    TP53 (Tumor protein P53) • CD34 (CD34 molecule) • HSPA9 (Heat Shock Protein Family A (Hsp70) Member )
    |
    Chr del(5q) • TP53 expression
    10ms
    MBG453 in Lower Risk MDS (clinicaltrials.gov)
    P2, N=20, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2022 --> Jan 2026 | Trial primary completion date: Jun 2022 --> Jun 2024
    Enrollment open • Trial completion date • Trial primary completion date
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    Chr del(5q)
    |
    sabatolimab (MBG453)
    10ms
    Myelodysplasia-related gene mutations are associated with favorable prognosis in patients with TP53-mutant acute myeloid leukemia. (PubMed, Ann Hematol)
    The complete response rates for intensive chemotherapy (IC), hypomethylating agent (HMAs)-based therapies, and azacitidine plus venetoclax were 35.7%, 22.2%, and 37.5%, respectively. In conclusion, patients with TP53-mutant AML have poor prognoses under current treatment strategies and MR gene mutations are associated with a more favorable survival. Therefore, further studies are needed to improve the survival rates in this population.
    Journal
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    TP53 (Tumor protein P53)
    |
    TP53 mutation • Chr del(5q) • Chr del(7q)
    |
    Venclexta (venetoclax) • azacitidine
    10ms
    Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    Chr del(5q)
    |
    etoposide IV • busulfan • cyclosporine
    11ms
    Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)
    P1, N=100, Recruiting, Jacqueline Garcia, MD | Trial completion date: Dec 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    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) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • MLL rearrangement • U2AF1 mutation • Chr del(5q) • FLT3 wild-type
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    Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan
    12ms
    The der(1;7)(q10;p10) defining a distinct profile from -7/del(7q) in myelodysplastic syndromes: A systematic review and meta-analysis. (PubMed, Cancer Med)
    The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.
    Retrospective data • Review • Journal
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    TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • ETNK1 (Ethanolamine Kinase 1)
    |
    TP53 mutation • Chr del(5q) • Chr del(7q)
    1year
    Collaborative effect of Csnk1a1 haploinsufficiency and mutant p53 in Myc induction can promote leukemic transformation. (PubMed, Blood Adv)
    Downregulation of Myc protein expression correlated with efficient elimination of blasts in A51 treatment. The "myc signature" closely resembled the transcriptional profile of del(5q) MDS patients with TP53 mutation.
    Journal
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CSNK1A1 (Casein Kinase 1 Alpha 1) • EGR1 (Early Growth Response 1)
    |
    TP53 mutation • MYC expression • Chr del(5q)
    1year
    DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML. (PubMed, Leukemia)
    Here, we showed that the partial loss of DELE1 expression observed in -5/del(5q) patients was sufficient to significantly reduce the sensitivity to mitochondrial stress in AML cells. Overall, our results suggest that DELE1 haploinsufficiency could represent a new driver mechanism in -5/del(5q) AML.
    Journal
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    TP53 (Tumor protein P53) • ATF4 (Activating Transcription Factor 4)
    |
    TP53 mutation • Chr del(5q)
    1year
    Pulmonary infection associated with immune dysfunction is associated with poor prognosis in patients with myelodysplastic syndrome accompanied by TP53 abnormalities. (PubMed, Front Oncol)
    The complete response rates for azacitidine monotherapy, venetoclax combined with azacitidine, decitabine monotherapy, and decitabine combined with low-dose chemotherapy were 9.1%, 41.7%, 37.5%, and 33.3%, respectively. In conclusion, TP53 abnormalities in patients with MDS were frequently accompanied by complex karyotypes, and treatments based on hypomethylating agents or venetoclax have limited efficacy. Pulmonary infections associated with immune dysfunction is associated with poor prognosis.
    Journal
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    TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    Chr del(5q) • Chr del(7q)
    |
    Venclexta (venetoclax) • azacitidine • decitabine
    1year
    Cytogenetics in the management of myelodysplastic neoplasms (myelodysplastic syndromes, MDS): Guidelines from the groupe francophone de cytogénétique hématologique (GFCH). (PubMed, Curr Res Transl Med)
    A karyotype on bone marrow remains mandatory at diagnosis of MDS with complementary molecular analyses now required. Analyses with FISH or other technologies providing similar information can be necessary to complete and help in case of karyotype failure, for doubtful CA, for clonality assessment, and for detection of TP53 deletion to assess TP53 biallelic alterations.
    Clinical guideline
    |
    TP53 (Tumor protein P53)
    |
    TP53 deletion • Chr del(5q) • Chr del(7q)
    1year
    TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q). (PubMed, Br J Haematol)
    Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.
    Journal
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    TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
    |
    SF3B1 mutation • Chr del(5q)
    1year
    Salvage Autologous Peripheral Blood Stem Cell Transplantation after the Development of tMDS or AML in Multiple Myeloma Patients (ASH 2023)
    Post transplant treatment included lenalidomide maintenance, followed by a variety of salvage regimens over the next 7 years including thalidomide, carfilzomib, daratumumab and pomalidomide...He received a second ASCT after melphalan 140 mg/m2 in Oct 2017 followed by recovery of normal blood counts...Case 3 = 65-year-old man with MM treated with bortezomib + dexamethasone followed by ASCT in Aug 2012...Six months of decitabine did not improve his blood counts...This approach was well tolerated and provided durable hematopoietic recovery. Second ASCT using banked autologous stem cells should be considered in such patients who are not otherwise candidates for allogeneic transplantation.
    Clinical
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    TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SETBP1 (SET Binding Protein 1)
    |
    TP53 mutation • Chr del(17p) • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • Chr del(5q)
    |
    lenalidomide • bortezomib • decitabine • Darzalex (daratumumab) • carfilzomib • dexamethasone • pomalidomide • thalidomide • melphalan
    1year
    Identification of Vulnerabilities for Pharmacological Inhibition of PIP4K2s in Acute Myeloid Leukemia (ASH 2023)
    Kasumi-1, NB4 and U-937 cells were treated with vehicle or increasing concentrations of THZ-P1-2 and/or venetoclax for 48h... Our study characterized the expression of PIP4K2s in the myeloid compartment of hematopoietic cells, as well as in different molecular subsets of AML. The identification of the correlation between the expression of PIP4K2s and the response to antineoplastic agents in ex vivo assays in AML exposed vulnerabilities that can be exploited in combined therapies, which could result in better therapeutic responses. Support by FAPESP, CNPq, and CAPES.
    PARP Biomarker
    |
    CD34 (CD34 molecule) • ANXA5 (Annexin A5)
    |
    Chr del(5q)
    |
    Venclexta (venetoclax)
    1year
    Emergence of TP53 mutation during lenalidomide therapy of myelodysplastic syndrome with del(5q) and its subsequent disappearance following salvage therapy with decitabine. (PubMed, Haematologica)
    Not available.
    Journal
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    TP53 (Tumor protein P53)
    |
    TP53 mutation • Chr del(5q)
    |
    lenalidomide • decitabine
    1year
    Recent findings in myelodysplastic syndrome (PubMed, Dtsch Med Wochenschr)
    The IPSS-M also represents an important extension with regard to prognosis estimation for patients with therapy-related MDS.In 2020 Luspatercept has been approved for transfusion-dependent lower risk MDS patients harboring ring sideroblasts ± an SF3B1 mutation after failure of an erythropoiesis stimulating agent. In addition, data from the phase III trial with Imeltelstat give reason to hope that we will be able to offer a new second-line therapy to LR-MDS patients. For higher risk MDS patients azacitidine therapy remains the standard of care, results of phase III trials of combination therapies must be awaited.
    Journal
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    TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
    |
    SF3B1 mutation • Chr del(5q)
    |
    azacitidine • Reblozyl (luspatercept-aamt)
    1year
    Comparison of the Revised 4 Th (2016) and 5 Th (2022) Editions of the World Health Organization (WHO) Classification in a Cohort of Patients with Lower-Risk Myelodysplastic Syndromes/Neoplasms (MDS) – a Glam Registry (REGLAM) Analysis (ASH 2023)
    Our study, to our knowledge, provides one of the first, if not the first, datasets from LMIC to describe characteristics of IPSS-R lower-risk MDS pts and their re-classification and corresponding survival according to the WHO 2016 and 2022 classifications. Limited availability of molecular analysis in real-life settings (e.g., TP53 mutations) highlights some of the challenges of using the 2022 WHO classification (as well as IPSS-M) LMIC. Understanding the epidemiology of MDS pts in LMIC is important especially as some of the newly approved agents for lower risk MDS are starting to be used in these countries.
    Clinical
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    TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
    |
    TP53 mutation • SF3B1 mutation • Chr del(5q) • Chr del(7q)
    1year
    Azacitidine Combination with Lenalidomide in Treating Higher-Risk Myelodysplastic Syndromes: A Single-Center, Phase 2 Trial (ASH 2023)
    Between Oct 2020 to Apr 2023, a total of 41 MDS patients were enrolled. 32 patients were evaluable for efficacy. 23 (71.875%) responded to therapy: 7 achieved a complete response (CR) (21.875%), 12 a marrow CR (mCR) (37.5%), and 4 a hematologic improvement (HI) (12.5%), of whom 10 of the mCR patients also had a HI.
    Clinical • P2 data
    |
    TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)
    |
    TP53 mutation • TET2 mutation • Chr del(5q)
    |
    lenalidomide • azacitidine
    1year
    A Clinical-Molecular Prognostic Scoring System for Myelodysplastic Syndrome in Asia – a Multicenter Study of the Asian Myeloid Working Group (AMWG) (ASH 2023)
    Three-hundred and ninety-four patients (32.2%) received hypomethylating agents (azaciticine, N=367; decitabine, N=27), and 158 patients (12.9%) underwent allogeneic haematopoietic stem cell transplantation... Combining genomic with hematological and cytogenetic parameters, the Asian clinical-molecular prognostic model improved the risk stratification of patients with MDS in Asia, potentially improving clinical decision-making.
    Clinical
    |
    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • SF3B1 mutation • PTPN11 mutation • Chr del(5q) • GNAS mutation
    |
    decitabine
    1year
    Data-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS) (ASH 2023)
    Table 2 shows a provisional, hierarchical classification algorithm. Further refinement of entity labels and classification criteria is the subject of the ongoing modified Delphi Process consensus approach among icMDS experts.
    TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • Chr del(5q) • Chr del(7q)
    1year
    Molecular Taxonomy of Myelodysplastic Syndromes and Its Clinical Implications (ASH 2023)
    The prognostic influence of bone marrow blasts varied in the individual genetic subgroups, suggesting that the clinical impact of increased blasts depends on the genetic context. The molecular taxonomy derived in this study is clinically relevant and will inform future classification schemas.
    Clinical
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • BCORL1 (BCL6 Corepressor Like 1)
    |
    TP53 mutation • TET2 mutation • U2AF1 mutation • Chr del(5q) • Chr del(7q) • TET2 deletion
    1year
    A Novel Prognostic Model for Patients with Acute Myeloid Leukemia in First Relapse with Improved Prognostic Accuracy (ASH 2023)
    In the GOELAMS model, 42% of intermediate risk patients were considered high (10%) or very high risk (32%) in the new model. Conclusion Analysis of clinical, cytogenetic and molecular variables identified nine variables for a new prognostic model which was associated with distinct OS at 1 year after first AML relapse and improved prognostic accuracy.
    Clinical
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    TP53 mutation • FLT3-ITD mutation • Chr del(17p) • DNMT3A mutation • Chr del(5q)
    1year
    Outcomes for Children with High Risk Acute Myeloid Leukemia on the Myechild 01 International Phase III Clinical Trial (ASH 2023)
    The MyeChild 01 international phase III trial (NCT02724163) in children with de novo AML allocated patients up to 3 doses of gemtuzumab ozogamicin (GO 3mg/m2/dose) during the first course of induction chemotherapy (mitoxantrone 12 mg/m2/dose x4; cytarabine 100 mg/m2/dose x20). Two intensive courses of induction chemotherapy, including GO and mitoxantrone in course 1 and FLA-Ida in course 2, consolidated with allogeneic HSCT, appears to be an effective approach for most HR patients. 2 year estimated outcomes for HR patients compare favourably to recent trials of GO in pediatric AML, with particularly encouraging data for patients with KMT2A-r and FLT3-ITD.
    Clinical • P3 data
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • AFF1 (AF4/FMR2 Family Member 1) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement • Chr del(5q) • MLL fusion
    |
    cytarabine • Mylotarg (gemtuzumab ozogamicin) • mitoxantrone
    1year
    Clinical and Molecular Characterization of Patients with Therapy Related Myeloid Neoplasms (TRMN) (ASH 2023)
    Our results highlight the role of mutations in cancer predisposition genes in the development of TRMN. Similar latency associations were found for TRMN and nTMN patients, which suggest that other risk factors different than treatment might contribute to the TRMN development. Altered karyotypes in TRMN patients are associated with acquired mutations in myeloid genes but not with germline mutations, which suggests two different entities with different prognosis.
    Clinical • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2)
    |
    CHEK2 mutation • Chr del(5q) • PMS2 mutation
    1year
    Clinical, Cytogenetic and Immunophenotypic Spectra of Post-Transplant Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome (ASH 2023)
    Post-HCT relapse treatments included hypomethylating agents (HMA; n=13/46, 28%), HMA with donor lymphocyte infusion (DLI; n= 7/46, 15%), HMA with Venetoclax (VEN; n=7/46, 15%), chemotherapy (n=9/46, 19%), best supportive care (8/46, 17%) and second HCT (n=2/46, 4%)...The relapsed disease often shows evidence of clonal evolution in its immunophenotype and/or cytogenetic profile toward a more aggressive disease. Approaches to post-HCT relapse remain heterogenous but HMA is beneficial.
    Clinical • Post-transplantation
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD34 (CD34 molecule) • CD7 (CD7 Molecule)
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    Chr del(5q) • Chr del(7q)
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    Venclexta (venetoclax)
    1year
    Impact of Typical and Atypical Complex Karyotype Subgroups on Outcome of AML Patients Undergoing Allogeneic Stem Cell Transplantation (ASH 2023)
    Within pts with a CKT receiving HSCT, we identified additional prognostic factors including the presence of ≥5 cytogenetic aberrations. These pts are in urgent need for novel post HSCT approaches.
    Clinical • IO biomarker
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    TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule) • ADGRG1 (Adhesion G Protein-Coupled Receptor G1)
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    TP53 mutation • RUNX1 mutation • Chr del(5q) • LDH-L • Chr del(7q)
    1year
    Characterization of MDS and CMML Patients Harboring Trisomy 8 Abnormality: Clinical, Autoimmune, and Mutational Features (ASH 2023)
    A total of 27 (7.6%) MDS/CMML patients with trisomy 8 (21 with trisomy 8 at baseline) were found to have a bona fide autoimmune disease, including autoimmune uveitis/scleritis (n=3), (rheumatoid and psoriatic), polyarteritis nodosa, giant cell arteritis with polymyalgia rheumatica, autoimmune sclerosing pancreatitis, immune hemolytic anemia, synovitis, and Grave's disease. Conclusions MDS/CMML with trisomy 8 showed unique clinicopathologic characteristics compared to MDS-NK: higher baseline BM blasts, higher representation of "Very High" IPSS-R risk categories with characteristic mutational signatures and a variety of underlying autoimmune diseases.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD8 (cluster of differentiation 8) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • STAG2 (Stromal Antigen 2)
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    KRAS mutation • Chr del(11q) • ASXL1 mutation • CD8 positive • Chr del(5q) • STAG2 mutation • WT1 overexpression
    1year
    Tracking of Leukemia and Immune Single Cell Phenotypes during Ipilimumab-Based Treatment By Long-Read Sequencing (ASH 2023)
    To better understand determinants of response and resistance of CTLA-4 blockade in AML, we applied nanoranger to bone marrow samples collected in the context of a phase I trial investigating combined decitabine and ipilimumab (NCT02890329). In sum, genotyping with nanoranger substantially augmented scRNA-seq analyses of ipilimumab-based therapy in bone marrow AML. This exemplifies the great potential that long-read sequencing-based single cell studies hold to better define response and resistance mechanisms of novel immunotherapies.
    IO biomarker
    |
    DNMT3A (DNA methyltransferase 1) • CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    TP53 mutation • DNMT3A mutation • Chr del(5q) • PTPRC expression • CTLA4 expression
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    Yervoy (ipilimumab) • decitabine