Abnormal glucocorticoid receptors in acute leukemia cells.
In normal tissues, 3H-triamcinolone acetonide (3H-TA) labeled glucocorticoid receptors can be resolved into 2 components by DEAE chromatography: peak I elutes at 0.04 M salt and peak II at 0.22 M salt. By glycerol gradient centrifugation, peak I is 3.5S and peak II is 8.5S. Peak I binds to DNA, while peak II does not. Blast cell 3H-TA-binding macromolecules in 27 of 62 cases of acute leukemia had DEAE binding characteristics identical to those of normal tissues; the remaining 35 cases were abnormal. In these cases there was either a single DEAE species eluting in the peak I area (30 cases) or multiple low-amplitude peaks eluting across the entire gradient (5 cases). The abnormal single peak material failed to bind to DNA in 5 cases (of 5 studied), whereas peak I material from 5 cases (of 5 studied), showing normal peak I-peak II ratios, bound normally to DNA. In 3 cases (of 3 studied), the abnormal single peak material had an S value of 2-2.5S, whereas in 5 cases with normal peak I-peak II ratios, the S values were 3.5S and 8.5S, respectively. We hypothesize that those leukemias with abnormal binder characteristics cannot respond to glucocorticoid therapy.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D002482:Cellulose; D002499:Centrifugation, Density Gradient; D002648:Child; D002675:Child, Preschool; D002845:Chromatography / Q000379:methods; D002848:Chromatography, DEAE-Cellulose; D004247:DNA; D004351:Drug Resistance; D006358:Hot Temperature; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D002482:Cellulose; D004247:DNA