title: Amplification of BCR-ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia.
abstract: The Philadelphia (Ph) chromosome, or t(9;22), is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene (previously ABL) on chromosome 9. CML is clinically characterized by three distinct phases: chronic, accelerated, and blast phase. Blast crisis is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), with secondary chromosomal abnormalities present. We report a case of myeloid blast crisis of CML resistant to imatinib mesylate and chemotherapy. By use of cytogenetic, fluorescence in situ hybridization, and comparative genomic hybridization methods, we identified a cluster of BCR-ABL amplification on inverted duplication of the Ph chromosome with t(3;21)(q26;q22) and increased genomic levels of the RUNX1 gene (previously AML1). The t(3;21)(q26;q22) is a recurrent chromosomal abnormality in some cases of CML blast phase and in treatment-related myelodysplastic syndrome and acute myeloid leukemia. Amplification or copy number increase of RUNX1 has been reported in childhood acute lymphoblastic leukemia. Our study indicated that the progenitor of CML was BCR-ABL dependent through the amplification of Ph chromosome as a mechanism of resistance to imatinib therapy. The coexistence of BCR-ABL and t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML blast transformation.
authors: Department of Hematology, Hospital Ampang, Jalan Megah Utara, Pandan Mewah, 68000 Ampang, Selangor, Malaysia. cuapcl@hotmail.com
authors: Chin-Lee
authors: CL
authors: Phan
authors: Puteri J N B
authors: PJ
authors: Megat Baharuddin
authors: Lai-Peng
authors: LP
authors: Chin
authors: Zubaidah
authors: Z
authors: Zakaria
authors: Subramanian
authors: S
authors: Yegappan
authors: Jameela
authors: J
authors: Sathar
authors: Sen-Mui
authors: SM
authors: Tan
authors: Visalachy
authors: V
authors: Purushothaman
authors: Kian-Meng
authors: KM
authors: Chang
mesh_terms: D000328:Adult; D001752:Blast Crisis; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D016044:Fusion Proteins, bcr-abl