HAEM5:B-lymphoblastic leukaemia/lymphoma with hypodiploidy: Difference between revisions

The clinical features are generally similar to those seen in other types of B-ALL like anemia, thrombocytopenia and neutropenia. May have very high WBC count at presentation. Malignant and poorly differentiated lymphoid cells in the bone marrow, peripheral blood and extramedullary sites<ref name=":1">{{Cite journal|last=Terwilliger|first=T.|last2=Abdul-Hay|first2=M.|date=2017|title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update|url=https://www.ncbi.nlm.nih.gov/pubmed/28665419|journal=Blood Cancer Journal|volume=7|issue=6|pages=e577|doi=10.1038/bcj.2017.53|issn=2044-5385|pmc=5520400|pmid=28665419}}</ref>. Symptoms may include anemia, thrombocytopenia, leukopenia, fever, weight loss, night sweats, bleeding, bruising, fatigue<ref name=":1" />.  Splenomegaly and hepatomegaly (20%), central nervous system (CNS) in 5-8% of patients<ref name=":1" />.  Diagnosis: 20% of blasts or more lymphoblasts in the bone marrow, or peripheral blood<ref name=":1" />.

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==Sites of Involvement==

N/A

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is the most common cause of cancer in pediatric patients. It is characterized by recurrent genetic abnormalities of chromosome number, deletions, duplications and translocations. Hypodiploidy, a neoplasm of lymphoblasts containing less than 46 chromosomes<ref name=":0" />. Hypodiploid ALL has poor prognosis and near haploid with worst prognosis<ref name=":0" /><ref name=":2" /><ref name=":3">{{Cite journal|last=Nachman|first=James B.|last2=Heerema|first2=Nyla A.|last3=Sather|first3=Harland|last4=Camitta|first4=Bruce|last5=Forestier|first5=Erik|last6=Harrison|first6=Christine J.|last7=Dastugue|first7=Nicole|last8=Schrappe|first8=Martin|last9=Pui|first9=Ching-Hon|date=2007|title=Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/17473063|journal=Blood|volume=110|issue=4|pages=1112–1115|doi=10.1182/blood-2006-07-038299|issn=0006-4971|pmc=1939895|pmid=17473063}}</ref>.

In near haploid cases, two-thirds had activation of RAS signaling and P13K signaling pathways; these are sensitive to P13K inhibitors indicating these drugs may offer a new therapeutic option<ref name=":2" />.

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==Individual Region Genomic Gain / Loss / LOH==

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==Characteristic Chromosomal Patterns==

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'''Based on WHO classification'''<ref name=":0" />''', hypodiploidy is divided into:'''

The most significant observation by Holmfeldt et al.,<ref name=":2" /> is that a global difference in the gene expression profiles distinguishes subgroups of hypodiploid ALL. More than 600 genes had subtype specific enrichment on gene set enrichment analysis<ref name=":2" />. In addition, RAS pathway, ''RB1'' and ''TP53'' mutations mimic solid tumor pathways<ref name=":2" />.

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==Gene Mutations (SNV / INDEL)==

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'''''TP53'' mutations''': High mutation rate was observed (91%) in low hypodiploid than in non-low hypodiploid (5%) B-ALL; In low hypodiploid ALL, 43% were observed in non-tumor hematopoietic cells, suggesting either an inherited or a germline ''de novo'' origin of the mutation<ref name=":2" />.

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==Epigenomic Alterations==

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RTK and RAS pathway alterations as ''de novo'' germline mutations or in primitive hematopoietic progenitor cells<ref name=":2" />.

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==Genetic Diagnostic Testing Methods==