Ring chromosome derived from BCR/ABL in an acute lymphocytic leukemia

Abstract

A previously healthy 44-year-old female was referred to our hospital with an increase of peripheral white blood cell (WBC) counts and slight fever. CBC showed a hemoglobin level of 9.7 g/dL, a platelet count of 205 9 10/L, and WBC count of 128.4 9 10/L with 4 % segmented neutrophils, 5 % band form neutrophils, 4 % lymphocytes, 1 % monocytes and 86 % blasts. Bone marrow aspiration showed a hypercellular marrow (nuclear cell count: 542 9 10/L) with a massive increase of hematopoietic blasts (83.8 %). These blasts were negative for MPO and esterase. Flow cytometric analysis confirmed cells positive for CD10, CD19, and CD34, and negative for CD3, CD4, CD7, CD14, CD56, and CD8. G-banding analysis of chromosomes revealed 46XX, -9, -22, ?r1 in six of 20 metaphases (Fig. 1a) and fluorescent in situ hybridization (FISH) analyses demonstrated that the ring chromosome contained BCR/ABL fusion signals (Fig. 1b), which were detected in most metaphases (88 %). BCR/ABL transcripts were confirmed by qualitative reverse transcriptase-polymerase chain reaction and revealed minor bcr involvement. Upon these data, she was diagnosed with B lymphoblastic leukemia with t(9;22)(q34;q11.2); BCR/ABL based on the WHO classification. Ring chromosome is a circular structural chromosome abnormality that is assumed to arise from breakage and subsequent fusion of one or multiple chromosomes. This chromosomal abnormality is often unstable, leading to concomitant genetic loss or amplification. This may explain why ring chromosome is extremely rare in hematopoietic malignancies [1], although many other chromosomal abnormalities are frequently found. In this case, the FISH analysis showed multiple distinct BCR/ABL fusion signals in a ring chromosome, strongly suggesting that this ring chromosome is derived from Philadelphia chromosome t(9;22). There are several acute lymphoblastic leukemias carrying r(9)(q34q34) listed in the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, but these do not have BCR/ABL fusion [2]. This is the first case to our knowledge demonstrating the BCR/ABL fusion in a ring chromosome. It remains uncertain how this unique chromosomal structure contributes to clinical outcome. Accumulation of leukemia patients with ring chromosome linking BCR/ABL is necessary to elucidate its contribution to clinical manifestation.