Four Cases of Chronic Myelogenous Leukemia in Mixed Phenotype Blast Phase at Initial Presentation Mimicking Mixed Phenotype Acute Leukemia with t(9;22)

The t(9;22)(q34;q11.2) translocation results in a BCR-ABL1 fusion gene located on the Philadelphia chromosome (Ph), causing a constitutively active BCR-ABL1 tyrosine kinase. This fusion gene is found in virtually all cases of CML, 5% of pediatric and 15-30% of adult cases of ALL, and 1-2% of cases of de novo AML [1-3]. While mixed phenotype acute leukemia (MPAL) with t(9;22)(q34;q11.2) is rare, this translocation is the most common recurrent genetic abnormality seen in MPAL [4]. Untreated CML typically follows a biphasic or triphasic clinical course. An initial indolent chronic phase (CP) is followed by an accelerated phase (AP) and/or a blast phase (BP) [5]. Only about 10% of patients initially present in BP [6]. Such cases can be easily misdiagnosed as acute leukemia with t(9;22) [4]. In about 70% of CML-BP cases, the blast lineage is myeloid, whereas the blasts are lymphoblasts in 20-30% of cases [5]. In addition, the blasts are of mixed phenotype only in rare cases of CML-BP [7]. Here, we report 4 cases of CML in mixed phenotype BP, diagnosed by FISH analysis performed on mature neutrophils, which were initially suspected to be acute leukemia with t(9;22). Splenomegaly, major BCR-ABL1, and peripheral granulocytic hyperplasia with all stages of granulocytes without dyspoiesis were observed in all cases. The clinical and laboratory findings at initial presentation are summarized in Table 1. CASE 1: A 60-yr-old man presented with fatigue, myalgia, chills, dull pain in the left axillary region, and weight loss of 5 kg over 15 days. Ultrasonography revealed splenomegaly. Laboratory tests showed white blood cell (WBC) count of 41.9×10/L, Hb level of 11.2 g/dL, and platelet count of 74×10/L. Peripheral blood (PB) smear revealed granulocytic hyperplasia, 17% blasts of moderate size, and 2% basophils. Bone marrow (BM) aspirates revealed 100% cellularity with 68% blasts. Following the preliminary diagnosis of MPAL with t(9;22), the patient was started on ALL-type induction chemotherapy. A cytogenetic study showed 46,XY,t(9;22)(q34;q11.2) in all 30 cells analyzed with additional chromosomal aberrations. FISH analysis using BCR/ABL1 probe (Abbott Molecular/Vysis, Des Plaines, IL, USA) showed fusion signals in 95% of the cells analyzed. In addition to blasts, mature neutrophils also revealed BCR-ABL1 signals. Therefore, a final diagnosis of CML in mixed phenotype BP was made.