HOMEOPROTEINS - CONTRIBUTION TO THE HEMATOPOIETIC PROCESSES

The molecular basis of commitment and differentiation of hematopoietic cells remain poorly understood at the genetic level. Among putative c andidates involved in these processes are homeoproteins, a large famil y of transcription factors which play a major role during development. Using a srategy based on the polymerase chain reaction (PCR) we have isolated nine different Antennapedia-like homeobox (HOX) genes from pu rified human hematopoietic precursors. Their expression patterns, anal yzed with a panel of leukemia-derived cell lines representing various blood cells phenotypes, appears to be lineage-restricted. Extending ou r study to all the known members of the HOX 1 and HOX 2 clusters, we f ound that HOX 1 genes are predominantly detected within cells of myelo monocytic origin whereas HOX 2 genes transcripts are principally expre ssed in erythro-megakaryocytic cell lines. Furthermore, we have observ ed that the expression of three HOX 1 genes within B lymphoid lineages is stage-related and that the expression of several of them is switch ed off during TPA-induced differentiation of KG1 and U937 cells. These observations support the idea that homoproteins could be regulators o f lineage determination during hematopoiesis.