A Case with Coexistence of Major and Minor BCR/ABL Fusion Transcript at Lymphoblastic Crisis of Chronic Myelogenous Leukemia in Patients with Major BCR/ABL Positivity during Chronic Phase

Dear Editor CML is characterized by the clonal expansion of bone marrow hematopoietic cells and is associated with the Philadelphia chromosome [1]. The accelerated phase of CML, which is also known as the blast crisis phase, occurs in patients as the disease progresses. It has been reported that the appearance of an additional chromosomal abnormality is the major pathogenic factor in 63% of the CML cases [2, 3]. However, the additional appearance of a minor BCR/ABL fusion transcript with disease progression has rarely been reported in CML patients. Moreover, the dual expression of the major and minor BCR/ABL fusion transcripts during blast crisis has been reported in only 4 cases to date [4, 5]. Here, we describe a CML patient who exhibited the dual expression of the major and minor BCR/ABL fusion transcripts during the lymphoblastic crisis (LBC) phase and possessed a mutation in the BCR/ABL kinase domain. A 13-yr-old boy was admitted to Asan Medical Center in June 2010 for severe leukocytosis and anemia (white blood cell [WBC] count: 464.1×10/L: hemoglobin: 68 g/L), and splenomegaly. Bone marrow aspiration and biopsy findings were indicative of CML, with 5.4% of myeloblasts demonstrating granulocytic hyperplasia. His karyotype was 46,XY,t(9;22)(q34;q11.2)[20]. FISH analysis for the detection of the BCR/ABL fusion transcript showed nuc ish (ABL1, BCR)×3 (ABL1 con BCR×2)[190/200]. We performed reverse-transcriptase PCR for the detection of the major and minor BCR/ABL fusion transcripts but were able to detect only the major BCR/ABL fusion transcript (b2a2 type). Quantification analysis using the LightCycler t(9;22) Quantification Kit (Roche Diagnostics, Mannheim, Germany) showed a ratio of 8.00 (normalized copy number, NCN) for the major BCR/ ABL transcript. The patient was thus diagnosed with chronic phase CML, and imatinib treatment was initiated. The patient demonstrated a partial hematologic response for 2 yr after the treatment was started. In June 2012, the patient was readmitted because he had poor oral intake and diarrhea. A complete blood count (CBC) revealed mild leukocytosis (WBC count: 16.1×10/L) with 47% blasts in peripheral blood and 48% lymphoblasts in bone marrow aspirates. Immunophenotyping results indicated B-cell acute lymphoblastic leukemia. At this time his karyotype had changed to 45,XY,-7,t(9;22)(q34;q11.2)[20], indicating the appearance of monosomy 7. FISH analysis revealed nuc ish (ABL1×2, BCR×3)(ABL1 con BCR×1)[168/200], indicating that 84.0% of the cells showed BCR-ABL rearrangement with 5’ ABL1 dele-