We reported here an AML patient with the malignant cells carrying a novel rearrangement, a t(6;14)(q25~q26; q32.2). The breakpoint on chromosome 14 was narrowed with FISH to a single BAC containing the BCL11B gene (Figs. 1 and 3). Lack of further material precluded either narrowing the rearrangement on chromosome arm 6q or investigating the expression of BCL11B. Translocation (6;14)(q25;q32) has been previously reported in two cases of hematological malignancies, one involving a childhood acute mixed lineage leukemia (AMLL) and the other an acute nonlymphoblastic leukemia (ANLL)[16–18]. The AML of our patient (M1) and the rearrangement described here at the cytogenetic level are compatible with these reported cases, and it is plausible not only that all these patients carry similar chromosomal rearrangements but also that the presence of either mixed lineage or myelocytic lineage in a predefined FAB classification is related to the age of the patients.
The present study is the first report implicating
BCL11B(OMIM 606558) in AML. TheBCL11Bgene codes for an 823-amino-acid protein, which presents 61% homol- ogy to the protein product ofBCL11A(2p13; OMIM 600557) overall, but 95% homology in their zinc finger domains.
BCL11Ais a highly conserved gene across a wide range of species, and is rearranged and overexpressed in some chronic lymphocytic leukemia (CLL) patients[21,22].
This report calls attention to the possible role ofBCL11B
in the etiology of hematological malignancies and provides a candidate gene for AML (especially FAB-M1 cases), ANLL, and AMLL with apparently normal karyotypes.
Acknowledgments
This work was partially supported by Kreatech Biotech- nology (Amsterdam, The Netherlands). We thank M.J.M. van der Burg for her invaluable support in this work.
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