SELECTIVE EXPRESSION OF HEAT-SHOCK GENES DURING DIFFERENTIATION OF HUMAN MYELOID LEUKEMIC-CELLS

Several studies have indicated a role for heat shock proteins during d evelopment and differentiation. In these studies we have examined the patterns of activation of the HSP-70A, HSP-70B, HSP-70B' and HSP-28 mR NAs and proteins during the differentiation of immature human leukemic cells to more mature progenitors by several differentiation-inducing agents. K562 cells activate the mRNA for HSP-70A, HSP-70B' and HSP-28 genes in the presence of hemin or sodium butyrate as cells differentia te into late erythroblasts. K562 cells become progressively more resis tant to killing by heat shock during their differentiation to late ery throblasts. Further, selective inhibition of HSP-70A by antisense olig onucleotides to reduce HSP-70 kDa accumulation results in consistent r eduction of hemoglobin production by 25-30% in K562 cells exposed to h emin. HL-60 cells differentiate into mature macrophages within 3 days foliowing addition of PMA. HSP-70A m RNA levels increase with in the f irst 2 h of PMA treatment and remain elevated for up to 3 days during the cells' gradual differentiation into mature macrophages. PMA and so dium butyrate treatment also cause elevated levels of HSP-28 mRNA expr ession; this increase is barely detectable at 24 h but is considerable at 72 h when about 90% of HL-60 cells are differentiated into mature macrophages or monocytes. These studies show that HSP-70A, HSP-70B' an d HSP-28 may have specific roles during the differentiation of blood c ell progenitors into erythrocytes or macrophages. Further, differentia tion alters the thermal sensitivity of leukemic cells.