Among patients with adult acute lymphoblastic leukemia (ALL) the t(4;11) translocation (resulting in the MLL-AF4 fusion gene) is a recurrent chromosomal abnormality occurring in approximately 10–15% of cases. It is associated with poor outcome and in the majority of cases stem cell transplantation is the only possible cure. The MLL-AF4 cases show a more immature phenotype than other subtypes frequently lacking Ig light chain and/or TCR gene rearrangements (
Finally, mutations of FLT3 are detected in a large proportion of acute myeloid leukemias and in a small proportion of childhood ALL carrying the MLL-AF4 fusion gene while it has seldom been observed in adult ALL with t(4;11).
The aims of our study were twofold: 1) to expand on the initial observation that the VH6 gene rearrangement may be more frequent in adult patients carrying the t(4;11) translocation; 2). To assess the incidence of FLT3 mutations in an homogenous cohort of adult ALL patients carrying t(4;11) abnormality.
Thirty-two cases of MLL-AF4 fusion positive adult ALL patients (17M/15F) were analysed in addition to the RS4;11 cell line. Pro-B phenotype (n=11)predominated. Age ranged between 22–55 yrs(median: 32 yrs). Patients had cytogenetic or molecular evidence of t(4;11). The WBC count at presentation was high (60–550x109/l; median: 220). Patients were tested for VH gene rearrangement using FRI and consensus-JH primers. Internal tandem duplication and codon 835–836 kinase mutations of the FLT3 were screened by DNA PCR analysis.
Twenty-seven patients (84%) of the 32 tested carried a VH6 gene rearrangement. Of 36 IgH alleles, 27 (75%) were VH6 rearrangements. VH1 in 4 (11%) rearrangements was the second most common rearrangement while 3 were VH3 (8%) and 2 (5.5%) were VH4. Compared to our previous study (