BCL-X IS A REGULATORY FACTOR OF APOPTOSIS AND DIFFERENTIATION IN MEGAKARYOCYTIC LINEAGE CELLS

Differentiation- and lineage-related differences in the expression of two anti-apoptotic molecules, bcl-x and bcl-2, were examined using var ious human hematopoietic cell lines. Bcl-x was strongly expressed in c ell lines with erythroid and megakaryocytic properties (K562, HEL, CMK , and Mo7E), and was moderately expressed in immature myeloid cell lin es (KG-1 and KCL-22). Bcl-2 expression was relatively weak in these ce lls. On the other hand, bcl-x was not expressed in more mature myeloid cell lines (HL-60 and PL-21), but bcl-2 was strongly expressed in the se cells and in monocytoid cell lines (U937, THP-1, and JOSK-I). We in vestigated the biological significance of high levels of bcl-x express ion in erythroid and megakaryocytic lineage cells. When K562 cells wer e specifically differentiated into megakaryocytic lineage by phorbol e ster, the amounts of bcl-x increased by 10-fold. In contrast, bcl-x wa s gradually downregulated during erythroid differentiation induced by cytosine arabinoside. Apoptosis was observed following erythroid diffe rentiation of K562 cells, but it was not associated with megakaryocyti c differentiation in consistent with the increase in bcl-x. Moreover, phorbol ester-induced megakaryocytic differentiation was facilitated b y the overexpression of bcl-x in K562 cells. Finally, in situ hybridiz ation revealed that bcl-x mRNA expression was strongest in megakaryocy tes among normal bone marrow cells. These results suggest that bcl-x i s a regulatory factor in the apoptosis and differentiation of megakary ocytes.