Co-existence of isodicentric Ph chromosomes and the three-way Ph chromosome variant t(3;9;22)(p21;q34;q11) in a rare case of chronic myeloid leukemia

Abstract

Abstract. More than 90% of patients with chronic myeloid leukemia (CML) have the chromosomal translocation t(9;22)(q34;q11), while 5-8% of patients have complex variant translocations that have previously been thought not to affect the efficacy of imatinib therapy. The present study reports a patient with CML in B-lymphoid blast crisis who had a rare three-way Philadelphia (Ph) variant t(3;9;22)(p21;q34;q11), in addition to isodicentric Ph chromosomes. The patient was initially treated with imatinib for >2 months with a very poor response. When no T315I or F317L mutations in the ABL proto-oncogene 1 region were detected, the patient received dasatinib treatment (140 mg daily) and achieved a complete hematologic response. Following allo-hematopoietic stem cell transplantation, the patient displayed clinical, hematological and cytogenetic remission, with complete molecular response and complete donor chimerism, and stopped taking dasatinib at the last follow-up. The present data suggest that BCR-ABL gene amplification may be associated with imatinib resistance, which can be overcome with dasatinib. The present analysis suggests an alternative therapy strategy for CML involving isodicentric Ph chromosomes.

Patterns of chromosome abnormalities in a sample of Colombian patients with chronic myeloid leukemia

“…Structural abnormalities involving the long arm of chromosome 3, e.g., t(3;9;22)(q21;q34;q11.2), have been associated with poor prognosis and decreased survival [6]. The 3q21 chromosome region harbors tumor suppressor genes H37, Luca15, RBM5, and RASSFIA, and tumor susceptibility genes like the hMLH1 [8].…”

“…Some authors have suggested that these variants can arise through two mechanisms: the first, whereby three chromosomes simultaneously break, and the second, in which another chromosome attaches to a standard t (9;22) as a product of a clonal evolution. This second scenario is related to a poor prognosis [7,8]. Similarly, additional chromosomal alterations (ACAs) occur in approximately 5 % of CML cases.…”