HETEROGENEITY OF T(1-19)(Q23-P13) ACUTE LEUKEMIAS

The t(1;19)(q23;p13) translocation occurs commonly in B-lineage ALL. P revious reports have demonstrated a predominance of cases with express ion of cytoplasmic Ig mu (C mu(+)), an FAB L1/L2 phenotype, a poor pro gnosis and expression of a fusion transcript involving the E2A and PBX 1 genes in C mu(+) but not in C mu(-) cases. Of 38 patients with karyo typically proven t(1;19) (q23;p13) leukaemias, we extensively analysed 18 patients with acute leukaemia including 16 B-lineage Ws, one T-ALI , and one AML M4. The AML was associated with a classic E2A-PBX1 fusio n transcript and may represent the human counterpart of the AMLs induc ed by E2A-PBX1 retroviral infection of murine marrow progenitors. The T-ALL was E2A-PBX1 negative and neither the E2A nor the LYL-1 genes, b oth situated at chromosome 19 p13, were rearranged. Of the 16 B-lineag e Ws, four had cytological features resembling an 'L3-like' phenotype classically associated with Burkitt's lymphoma, two at diagnosis and r elapse and two exclusively at relapse, E2A-PBX1 fusion transcripts wer e detected by RT-PCR in all 13 C mu(+) patients and in 2/3 C mu(-) cas es. The 'L3-like' phenotype did not correlate with a particular stage of maturation arrest (one sIg(+), one C mu(+), one C mu(-)) or type of E2A-PBX1 transcript, but was associated in all cases with a trisomy 8 . Translocation, rearrangement, amplification or over-expression of th e c-myc gene was not observed in these cases, demonstrating that the a pparent association with trisomy 8 is not due to deregulation of this gene. We therefore show that the E2A-PBX1 transcript, although occurri ng predominantly in C mu(+) pre-B ALL, also occurs in C mu(-) early pr e-B ALL, sIg(+) B-W and even in AML. These results suggest, that the s tage of maturation arrest, and indirectly the prognosis, are not solel y due to the type of fusion transcript associated with the t(1;19).