Cytogenetic and immunogenotypic alterations of blast crisis cells in chronic myelogenous leukemia independently linked to immunophenotypic expression

Abstract

Chronic myelogenous leukemia (CML) is a disease of the hematopoietic stem cells, which can differentiate into either B-lymphoid or myeloid cells, because most of them develop either lymphoid or myeloid blast crisis. Immunophenotypic, genotypic, and cytogenetic analyses of 22 patients (24 episodes) with Philadelphia (Ph) positive CML in blast crisis were performed to determine the genetic alterations of the blast crisis cells. In B-lymphoid blast crisis, all the five patients had immunoglobulin heavy-chain (IgH) rearrangements and most of them showed normal karyotypes. Among the five patients, T-cell receptor (TCR) genes were rearranged at the following occurrence rates: 20% in TCR-beta, 60% in TCR-gamma, and 40% in TCR-delta chain genes. A high incidence of additional chromosome changes was noted in patients with B-lymphoid/myeloid-mixed blast crisis, but about 80% of them had rearranged IgH and about 40% had TCR rearrangements. In contrast, most of the patients with non-lymphoid blast crisis showed further chromosomal abnormalities, including +8, +19, i(17q), and double Ph, and most of them had germline configurations of IgH and TCR-gamma chain genes. Notably, only one patient (dual lymphoid and myelomegakaryoblast crisis) in this group exhibited IgH rearrangement, and TCR-beta and TCR-delta rearrangements were also rarely noted. Rearrangement of the IgH gene in CML blast crisis might be linked to expression of lymphoid markers, especially CD19.