THE GENOMIC LANDSCAPE OF HYPODIPLOID ACUTE LYMPHOBLASTIC LEUKEMIA
By L. Holmfeldt, Lei Wei, E. Diaz-Flores, M. Walsh, Jinghui Zhang, L. Ding, D. Payne-Turner, Michelle L. Churchman, A. Andersson, Shann-Ching Chen and 53 more. Nature Genetics, 2013
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The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24–31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32–39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
Subfields: Hematology, Public Health, Environmental and Occupational Health, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/fa0d1a9a72ea6bb08a5c1758efd0630fe38a5940
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In Public Health, Environmental and Occupational Health
In Pulmonary and Respiratory Medicine
Citations in the corpus
- The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. (2016, neutral): “In addition, the classification of hypodiploid B-ALL now highlights the unique association between low hypodiploid ALL and TP53 mutations that are often constitutional.(115,116) B-ALL with intrachromosomal amplification of chromosome 21.”
- Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. (2015, background): “Inherited Genetic Determinants of Leukemogenesis Children with certain constitutional genetic abnormalities (eg, trisomy 21) are at increased risk of developing ALL, and inherited mutations in TP53 and PAX5 have also been described recently in familial (as well as sporadic) ALL.(41,60) However, the ”