Clonal Evolution of t(8;21) Coexisting with t(9;22) in a Blastic Transformation of Chronic Myeloid Leukemia

Abstract

Abstract Introduction/Objective Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by chromosomal translocation t(9;22) and the production of the fusion protein BCR-ABL1. The clinical course of the disease is characterized by a chronic phase, accelerated phase, and blast phase. One of the criteria for the progress of chronic phase to accelerated phase is the presence of cytogenetic anomaly additional to t(9;22). The blast phase of CML usually presents as acute myelogenous leukemia (AML); however, its characteristics are different from de novo AML. One of the most common subtypes of de novo AML with balanced translocation is AML with t(8;21). Here, we present a case of the blast phase of CML that presents t(8;21). Methods/Case Report The peripheral blood from a 51-years-old-man presenting with fatigue and splenomegaly showed leukocytosis, mild anemia, marked neutrophilia with left shift, monocytosis, basophilia, and <1% blasts. Flow cytometry identified an increase in granulocyte events with the left shift. Chromosome studies detected t(9;22) by karyotyping and FISH. BCR-ABL1 transcript was detected at 41.98% on the International Scale by RT-PCR, consistent with chronic myeloid leukemia (CML). The following bone marrow biopsy confirmed a diagnosis of the chronic phase of CML with <5% myeloblasts. After a year of treatment with imatinib, the patient developed marked leukocytosis, anemia, and thrombocytopenia. Flow cytometry detected an immature cell population comprising ~50% of total cells positive for CD117, CD34 (partial), CD13 (dim), and CD33. A few blasts were also positive for cMPO and negative for CD14, CD64, TdT, Glycophorin A, cytoplasmic CD3, CD19, and other markers. BCR-ABL1 transcript was detected at 56.45% on the International Scale by RT-PCR. Chromosome analysis revealed all cells (20/20) exhibiting t(8;21) leading to a fusion between RUNX1 and RUNX1T1 genes with a maintained t(9;22). FISH analysis confirmed t(8;21) and t(9;22). These findings were consistent with a blast phase of CML. Results (if a Case Study enter NA) NA Conclusion Progression of CML is frequently accompanied by cytogenetic evolution. However, the development of t(8;21) in Ph+ clones is extremely rare. Only six cases have been previously reported. Misidentifying this blast phase of CML (in the absence of a clinical history of the chronic phase of CML) as AML with recurrent genetic abnormalities is a potential pitfall we should be aware of.