3e034f1fb6f90c444a8d2d8ddcb57512 pmc_35008193.pdf d434efb79f303c58f1a660ae4e05a60ff4377e45 pmc_35008193.pdf 19afd5c588dd0c8fe28241bde8310fd3c11278ec54f8753b13b6bb1f20cea63c pmc_35008193.pdf Title: Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much Subject: Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30–39 chromosomes) and near-haploidy (24–29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with <40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with <40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50–78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to “masked hypodiploidy”, which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients. -3pt Keywords: hypodiploidy; near-haploidy; B-cell acute lymphoblastic leukemia; clinical biomarkers; patient stratification Author: Oscar Molina, Alex Bataller, Namitha Thampi, Jordi Ribera, Isabel Granada, Pablo Velasco, José Luis Fuster and Pablo Menéndez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 27 04:09:37 2021 CET ModDate: Mon Dec 27 04:12:32 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1764663 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OGLZWV+VnURWPalladioL Type 1 Custom yes yes no 10 0 NQOPLC+URWPalladioL-Bold Type 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PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Definition of Hypodiploid B-ALL Subgroups Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Demographic Features of B-ALL with Hypodiploidy <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Clinical and Biological Features of B-ALL with Hypodiploidy <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Extramedullary Involvement at Presentation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Cytogenetic Characterization of B-ALL with Hypodiploidy <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Molecular Characterization of Hypodiploid B-ALL with <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Near-Haploid B-ALL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Low-Hypodiploid B-ALL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Proper Identification of Hypodiploid B-ALL with <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Etiology of Hypodiploidy in B-ALL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Origin of Near-Haploidy and Low-Hypodiploidy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Outcome and Treatment Strategies for B-ALL with Hypodiploidies <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Event-Free Survival and Overall Survival Rates Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Relationship of Genetic and Clinical Features with Patient Outcome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Current Treatment Protocols Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Novel Therapeutic Targets and Approaches to Treat B-ALL with <40 Chromosomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Concluding Remarks Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much Author: Oscar Molina, Alex Bataller, Namitha Thampi, Jordi Ribera, Isabel Granada, Pablo Velasco, José Luis Fuster and Pablo Menéndez Subject: Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30 39 chromosomes) and near-haploidy (24 29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with <40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with <40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50 78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to “masked hypodiploidy”, which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients. -3pt Keywords: hypodiploidy; near-haploidy; B-cell acute lymphoblastic leukemia; clinical biomarkers; patient stratification Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 27 04:09:37 CET 2021 ModDate: Mon Dec 27 04:12:32 CET 2021 ID: 0x203dc65fa91826513ddc5ada83e7863b, 0x203dc65fa91826513ddc5ada83e7863b Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: TGMGIM+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: TGMGIM+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 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