Precursor B cell lymphoid blast crisis of chronic myeloid leukemia with novel chromosomal abnormalities: A case report

Abstract

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder. It is characterized by the presence of the Philadelphia (Ph) chromosome, t(9;22)(q34.1;q11.2), which carries the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKIs) have markedly changed the treatment approach of CML and have become the first-line agents for almost all CML patients. However, certain patients experience resistance to these medications, which occurs through several mechanisms, including the accumulation of TKI-resistant chromosomal abnormalities. The present study reports a case of a 27-year-old Saudi male with CML receiving TKI treatment, who presented with precursor B-cell lymphoblastic crisis demonstrating the presence of the novel combined chromosomal abnormalities; non-Ph der(22), i(9) and der(20), carrying the BCR-ABL1 fusion gene. This case report adds to the literature on novel TKI-resistance-conferring chromosomal abnormalities and links them to precursor B-cell lymphoblastic crisis.

Keywords: blast crisis; chronic myeloid leukemia; cytogenetic abnormalities; precursor B cell; tyrosine kinase inhibitor.

Figure 1.

(A) Giemsa-banding karyogram of the patient's bone marrow. Isochromosome 9q, derivative chromosomes 20 and 22 (red arrows) are presented, where the extra material on 20 containing BCR-ABL1 fusion is derived from chromosome 22. (B) Ideogram of all chromosomal abnormalities observed in this case with breakpoints marked.

Figure 2.

FISH analysis of one metaphase and one interphase nucleus. (A) Showing two ABL1 (red) signals, one BCR signal (green), and two fusion gene BCR-ABL1 signals (yellow). (B) Labelled inverted image showing two ABL1 signals on the two long arms of isochromosome 9 (red), one BCR signal (green) on chromosome 22, and two fusion gene BCR-ABL1 signals (yellow) one on the long arm of der 9 and one on that of der 20, confirming the abnormalities seen on the karyogram. (C) Non-labelled inverted image identifying the chromosomes containing the signals.

Figure 3.

Ideogram illustrating the formation of the cytogenetic abnormalities observed in this case. (A) Ideogram of the proposed first step where a reciprocal translocation between chromosomes 9 and 22 (red arrows) formed the Philadelphia (Ph) and derivative (der) 9 chromosomes. (B) Ideogram of the proposed second step where a reciprocal translocation (bidirectional red arrow) between chromosome 20 and Ph chromosome formed der(22) and der(20) chromosomes (the latter carrying the BCR-ABL1 fusion gene). (C) Isochromosome 9q [i(9q)] formation as an additional cytogenetic abnormality that did not necessarily occur in this order.