Background and objective: The characteristic chromosomal translocation t(9;22)(q34;q11) in chronic myeloid leukaemia (CML) mainly results in the two different BCR/ABL fusion transcripts b2a2 or b3a2. Both transcript variants can occur simultaneously due to alternative splicing of the b3a2 transcript. Conflicting results have been reported on the influence of the transcripts on haematological findings at diagnosis and the course of the disease in adults while data concerning these topics on childhood CML are still missing. This paper reports on a correlation of BCR/ABL transcript variants with patients' characteristics in childhood CML.
Design and methods: Transcript types were determined in 146 paediatric patients with CML enrolled in trial CML-paed-I. Fifty-five patients (38%) expressed b2a2, 53 patients (36%) b3a2 and 38 patients (26%) both transcripts, respectively. These findings were correlated with patients' characteristics (sex, age, WBC, Hb, platelet count, hepatosplenomegaly, etc.) assessed at diagnosis.
Results: While the co-expression of both transcripts was evenly distributed among genders [b2a2 + b3a2: 22 females (28%), 16 males (24%)] a highly significant difference (P = 0.007) was found concerning the expression of the b2a2 transcript [34 male (51%) vs. 21 female (27%)] and vice versa of the b3a2 transcript [17 male (25%) vs. 36 female (45%)]. High platelet counts and the combination of high platelet counts in conjunction with pronounced leukocytosis were observed more often in patients expressing the b3a2 transcript.
Conclusions: These findings demonstrate that in children like in adults specific BCR/ABL transcript types present at diagnosis are associated with distinct haematological alterations (e.g. a high platelet count with the transcript b3a2). However, the sex-dependent skewed distribution of the BCR/ABL transcript types observed so far in this paediatric cohort only deserves further investigation.