The variant translocation of ABL1 Gene t(2;9)(q21;q34) in a childhood T-cell acute lymphoblastic leukemia

Abstract

Abstract:We present the case of the childhood ALL that was identifi ed by the translocation of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11) translocation. The observation of a poor clinical course of the case may contribute to explanation of the action of t(9;22)(q34;q11) translocation, of which poor prognostic action is known on ALL's, in terms of ABL1 gene, independent of the BCR gene. On the other hand, the prognostic signifi cance of this variant ABL1 translocation detection, which is very rarely observed, will cast a light on future cases (Tab. 1, Fig. 1 Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, which accounts for one third of all pediatric cancers. Some numerical and structural chromosomal abnormalities, including the translocations t(9;22)(q34;q11), t(12;21) (p13;q22), rearrangements of the MLL gene, hyperdiploidy and hypodiploidy are known as prognostic factors in the childhood ALL. Hyperdiploidy is defi ned as the gain of one or more chromosomes in a nonrandom fashion. In older children with B-precursor ALL, the two most common chromosomal abnormalities are high hyperdiploid (51-65 chromosomes or DNA index ≥1.16) and the t(12;21)(p13;q22) translocation, each observed in approximately one-third of cases. Whereas t(9;22)(q34;q11), rearrangements of the MLL gene translocations and hypodiploidy are well known to be poor prognostic factors, the translocation of t(12;21)(p13;q22) and hyperdiploidy is speculatively a good prognostic marker(1-5). The Abelson tyrosine kinase gene (ABL1) is located on chromosomal band 9q34. The main fusion partner of ABL1 gene is BCR (Breakpoint Cluster Region), involved in the t(9;22)(q34;q11), present in more than 95 % of patients with chronic myeloid leukemia, in 20 % of adults with pre-B ALL and in 2-3 % of childhood ALL (6).Furthermore, it is known that the ABL1 gene rarely translocates to chromosomes 1q24,14q32 and 10q22.3 (6-8). In generally, some chromosomal abnormalities are not found at diagnosis, but may develop after treatment. We report a very rare variant of ABL1 translocation involved in a t(2;9)(q21;q34), which may cast a light on prognosis of similar cases in future. Case reportA two-year-old girl was hospitalized at our department of pediatric hematology in May 2007 with a compliant of a nodule in the neck. During the physical examination, multiple lymphadenopathy, hepatosplenomegaly and skin related symptoms were detected. Hematological data were as follows: hemoglobin level 8 g/dl, white blood cell level 324 x 10 9 /l with 100 % blast cells and platelets at a level of 57 x 10 9 /l. Bone marrow aspirate showed hypercellularity with 100 % of lymphoblasts. Immunophenotyping showed results corresponding to T-ALL. The ALL BFM-95 treatment protocol was started. On day 8, steroid response was poor. The bone marrow examination was performed on day 15 and concluded as hypocellular. On day 30 of the treatment, the leukocyte level running earlier at a range of 3 x 10 9 /l -5 x 10 9 /l was identifi ed to rise up ...