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    BIOMARKER:

    Chr del(5q)

    1m
    Myelodysplastic syndromes: Updates on Genomic Landscape, Molecular Subtypes, & Targeted Therapies. (PubMed, Curr Hematol Malig Rep)
    Several recent targeted drug approvals including luspatercept and imetelstat have greatly expanded the treatment arsenal for lower-risk MDS. Standard of care therapy options for high-risk MDS, in particular TP53-mutated, remain limited beyond HMAs and transplant and are an active area of investigation.
    Review • Journal
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    TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SF3B1 (Splicing Factor 3b Subunit 1)
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    TP53 mutation • IDH1 mutation • Chr del(5q)
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    Reblozyl (luspatercept-aamt) • Rytelo (imetelstat)
    1m
    CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated Infusion With MDS and Secondary AML (clinicaltrials.gov)
    P1/2, N=19, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed
    Trial completion
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    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) • CALR (Calreticulin) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    TP53 mutation • Chr del(11q) • Chr del(5q)
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    cytarabine
    2ms
    LUSPLUS: Assessment of Effectiveness and Safety of Luspatercept in Patients Suffering From Lower-risk Myelodysplastic Syndrome. (clinicaltrials.gov)
    P3, N=70, Active, not recruiting, GWT-TUD GmbH | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Feb 2027 | Trial primary completion date: Dec 2024 --> Oct 2026
    Enrollment closed • Trial completion date • Trial primary completion date
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    SF3B1 (Splicing Factor 3b Subunit 1)
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    SF3B1 mutation • Chr del(5q)
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    Reblozyl (luspatercept-aamt)
    2ms
    MBG453 in Lower Risk MDS (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Nov 2026 | Trial primary completion date: Jun 2024 --> Nov 2024
    Enrollment closed • Trial completion date • Trial primary completion date
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    Chr del(5q)
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    sabatolimab (MBG453)
    3ms
    TP53 Expression Status Alters Hemoglobinization and Ferroptosis Sensitivity in K-562 Cells. (PubMed, Int J Mol Sci)
    However, terminal differentiation and hemoglobinization were significantly impacted in R175H mutant TP53-expressing K-562 cells. Findings from this work provide novel insights into the role of TP53 in lipid metabolism and terminal erythropoiesis.
    Journal
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    TP53 (Tumor protein P53)
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    TP53 mutation • TP53 wild-type • Chr del(5q)
    3ms
    Validation of clinicopathologic features of a genetic myelodysplastic syndrome classification in an independent cohort. (PubMed, J Hematop)
    The MDS-IWG molecular taxonomy of MDS is clinically applicable in routine practice and exhibits clinicopathologic and prognostic significance.
    Journal
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    TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • STAG2 (Stromal Antigen 2)
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    TP53 mutation • Chr del(5q)
    3ms
    Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)
    P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Recruiting --> Active, not recruiting
    Enrollment closed
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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) • 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)
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    TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)
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    Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan
    4ms
    A precision medicine approach to the myelodysplastic syndrome with isolated deletion 5q 50 years after its discovery. (PubMed, Blood)
    Lenalidomide can selectively suppress the del(5q)-mutant clone by promoting proteasomal degradation of casein kinase 1A1 and inducing mutant stem cell failure...Accurate assessment of the TP53 allelic state is crucial for distinguishing MDS-del(5q) from TP53-mutant MDS, a myeloid malignancy characterized by TP53 multihit state and very aggressive clinical course. Genomic profiling is also critical for therapeutic decision making in patients with MDS-del(5q), particularly for assessing a patient's eligibility for allogeneic transplantation, which remains the only curative treatment.
    Journal
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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) • TET2 (Tet Methylcytosine Dioxygenase 2) • CSNK1A1 (Casein Kinase 1 Alpha 1) • MIR145 (MicroRNA 145)
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    TP53 mutation • ASXL1 mutation • Chr del(5q)
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    lenalidomide
    4ms
    A clinico-genomic prognostic model for primary myelodysplastic neoplasm in Asia. (PubMed, Blood Cancer J)
    The APSS, compared with the International Prognostic Scoring System molecular (IPSS-M), showed superior concordance indices (C-indices) for OS (0.73 versus 0.57), LFS (0.72 versus 0.59), and TTP-sAML (0.75 versus 0.65) for this Asian cohort. In conclusion, the APSS enhanced prognostication of primary MDS in Asia.
    Journal
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    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)
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    TP53 mutation • RUNX1 mutation • Chr del(5q)
    4ms
    COALA: Impact of Optical Genome Mapping in Acute Myeloblastic Leukemia (clinicaltrials.gov)
    P=N/A, N=120, Completed, University Hospital, Bordeaux | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Dec 2024
    Trial completion • Trial completion date
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    TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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    Chr del(5q)
    5ms
    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: Feb 2026 --> Jun 2026 | Trial primary completion date: Aug 2025 --> Dec 2025
    Trial completion date • Trial primary completion date
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    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)
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    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • Chr del(5q)
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    cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
    6ms
    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: Apr 2025 --> Mar 2026
    Trial completion date
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    Chr del(5q)
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    etoposide IV • busulfan