Does BCR/ABL1 positive Acute Myeloid Leukaemia Exist?. (25th March 2013)

• Record Type: Journal Article
• Authors: Nacheva, Ellie P.; Grace, Colin D.; Brazma, Diana; Gancheva, Katya; Howard‐Reeves, Julie; Rai, Lena; Gale, Rosemary E.; Linch, David C.; Hills, Robert K.; Russell, Nigel; Burnett, Alan K.; Kottaridis, Panagiotis D.
• Is Part Of: British journal of haematology. Volume 161:Number 4(2013:May)
• Page Start: 541
• Page End: 550
• Publication Date: 2013-03-25
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12301
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12301-abs-0001"> <title>Summary</title> <p>The <italic>BCR/ABL1</italic> fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in <italic>de novo</italic> acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi‐lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the <italic>IKZF1</italic> and/or <italic>CDKN2A</italic> genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of 'hot spot' genome imbalances associated with <italic>BCR/ABL1</italic> positive pre‐B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the 'hot spot' regions to the Ph(+)AML and a further 40 <italic>BCR/ABL1</italic>(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to <italic>de novo </italic>Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar <italic>de novo</italic> Ph(+) AML and myeloid blast crisis of CML.</p> </abstract>