HEMATOPOIESIS A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1

Molecular events involved in specifica-tion of early hematopoietic system are not well known. In Xenopus, a paired-box homeodomain family (Mix.1-4) has been implicated in this process. Although Mix-like homeobox genes have been isolated from chicken (CMIX) and mice (Mml/ MIXL1), isolation of a human Mix-like gene has remained elusive. We have recently isolated and characterized a novel human Mix-like homeobox gene with a predicted open reading frame of 232 amino acids designated the Mix.1 homeobox (Xeno-pus laevis)–like gene (MIXL). The overall identity of this novel protein to CMIX and Mml/MIXL1 is 41 % and 69%, respectively. However, the identity in the homeodo-main is 66 % to that of Xenopus Mix.1, 79% to that of CMIX, and 94 % to that of Mml/ MIXL1. In normal hematopoiesis, MIXL expression appears to be restricted to immature B- and T-lymphoid cells. Sev-eral acute leukemic cell lines of B, T, and myeloid lineage express MIXL suggest-ing a survival/block in differentiation ad-vantage. Furthermore, Xenopus animal cap assay revealed that MIXL could in-duce expression of the -globin gene, suggesting a functional conservation of the homeodomain. Isolation of the MIXL gene is the first step toward understanding novel regulatory circuits in early hemato-poietic differentiation and malignant transformation. (Blood. 2002;100:89-95) © 2002 by The American Society of Hematolog