An unusual translocation, t(1;11)(q21;q23), in a case of chronic myeloid leukemia with a cryptic Philadelphia chromosome

Abstract

Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22)(q34;q11) [Philadelphia (Ph) chromosome). Although not frequently occurring, additional chromosome abnormalities (ACAs) can be detected at diagnosis and a number have been associated with an adverse cytogenetic and molecular outcome. The present study reports a case of CML presenting with the translocation t(1;11)(q21;q23) and a cryptic Ph chromosome. The presence of ACAs could generate greater genetic instability, promoting the emergence of further alterations. The present findings suggest that t(1;11)(q21;q23) can prevent a good response to tyrosine kinase inhibitor (TKI) therapy developing a primary resistance. In the present patient, at a recent follow-up, the T315I mutation was detected. This mutation confers full resistance to all available TKI, except ponatinib, which was not a therapeutic option due to comorbidities.

Keywords: MLL gene; additional chromosome abnormalities; chronic myeloid leukemia; cryptic Philadelphia chromosome; deletions on der(9).

Figure 1.

Metaphase showing translocation t(1;11)(q21;q23) and the add(9)(q34). The arrows indicate the chromosomes involved.

Figure 2.

(A) FISH of the breakpoint cluster region-ABL 1 gene (dual fusion-dual color). The white arrow indicates the Ph chromosome and the yellow arrow shows the chromosome der(9) with the residual ABL signal. (B) Painting FISH for chromosomes 1 and 11. The white arrow indicates the chromosome der(1) and the yellow arrow shows der(11). The absence of red or green signals on other chromosomes discounts a variant Ph, indicating an independent origin for the t(1;11)(q21;q23). Ph, Philadelphia; FISH, fluorescence in situ hybridization; ABL, Abelson murine leukemia viral oncogene homolog 1.