Detection of a histone‐2a related polypeptide in differentiated human myeloid cells (hl‐60) and its distribution in human acute leukemia

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Abstract
A human myeloid cell line, HL-60, has been shown to terminally differentiate to mature granulocytes in the presence of dimethylsulfoxide (DMSO) and other compounds. A histone polypeptide (HP) with an apparent molecular weight of 12,500 has been identified among the acid-extractable chromosomal proteins of DMSO-treated HL-60 cells. The detection of HP in total chromatin, total cell proteins or acid extracts of intact HL-60 cells treated with DMSO indicates that HP is present in intact cells and is not generated during the isolation procedures used for preparation of chromatin or histones. No radiolabelled HP was detected when chromatin was isolated from a mixture of radiolabelled mouse cells and HL-60 cells treated with DMSO. The relative increase in the amount of HP in DMSO-treated HL-60 cells correlates with a concomitant decrease of histone H2A. Fingerprint analysis of tryptic digests shows HP to be related to histone H2A. Generation of HP from endogenous and exogenous H2A is probably due to a proteolytic enzyme associated with the chromatin of the differentiated HL-60 cells. HP was not observed in chromatin from a number of human or mouse hematopoietic tissues and cell lines but low levels of HP were detected in human lymphocytes and granulocytes prepared from peripheral blood of normal donors. HP was also detected in leukocytes from patients with acute leukemia. Our results suggest that: (1) HP is a proteolytic product of histone H2A and not a product of an independent gene; (2) the observed level of HP in HL-60 cells is related to the stage of differentiation; and (3) HP is a potential biological marker for human acute leukemia.