Concomitant AID Expression and BCL7A Loss Associates With Accelerated Phase Progression and Imatinib Resistance in Chronic Myeloid Leukemia2016-12-20 15:37:39
Annals of Laboratory Medicine; 20 December 2016: /DOI:10.3343/alm.2017.37.2.177
Nae Yu, M.D., Saeam Shin, M.D., Jong Rak Choi, M.D., Yoonjung Kim, M.D., and Kyung-A Lee, M.D.
The mechanisms involved in chronic myeloid leukemia (CML) progression from the chronic phase (CP) to an accelerated phase (AP) or blast crisis (BC) remain largely undetermined, but generally involve additional molecular changes besides the Philadelphia chromosome . Evidence suggests that secondary BCR (breakpoint cluster region)-ABL1 (Abelson murine leukemia viral oncogene homolog 1)-dependent/independent genetic events play a critical role in blast transformation . Besides BCR-ABL1 point mutations, deletions and/or rearrangements of other cancer-related genes have been associated with CML-BC . Recent studies have demonstrated that aberrant activation-induced cytidine deaminase (AID) expression promotes genetic instability, eventually leading to progression and drug resistance in CML.
We report a patient with a rare chromosomal translocation 46,XY,t(5;12)(p13;p13) that disrupts AID and causes a concomitant deletion of the tumor suppressor gene BCL7A (B-cell CLL/lymphoma 7A). This report presents evidence of a mechanism underlying CML progression and tyrosine kinase inhibitor (TKI) resistance occurring through an interaction between AID expression and BCL7A loss in a BCR-ABL1 kinase domain mutation-independent manner.
A 57-yr-old man presented in December 2010 with generalized weakness and chest pain. Bone marrow (BM) demonstrated nearly packed marrow owing to myeloid and megakaryocyte hyperplasia (blasts [0.4%]). Written informed consent for genetic analysis was obtained from the patient according to the ethical guidance of the institutional review board. The patient exhibited the b3a2 type BCR-ABL1 fusion transcript, and cytogenetic analysis revealed a normal karyotype. The patient was diagnosed as having CML-CP and treated with imatinib.
Empire Genomic's AICDA Break Apart FISH Probe was used in this publication.
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