Expression of nuclear envelope lamins A and C in human myeloid leukemias.
The lamins are intermediate filament proteins that form a fibrous layer at the periphery of the nucleus. Experiments in cell-free systems have suggested that mammalian lamins A and C mediate an interaction between chromatin and the inner nuclear membrane that is essential for the reformation of the nucleus after mitosis. Other investigations, however, have suggested that lamins A and C are absent from myeloid cells and myeloid leukemia cell lines. To further investigate this apparent paradox, highly sensitive Western blotting techniques were utilized in the present study to examine the expression of lamins A and C in a series of human myeloid leukemia cell lines and in bone marrow samples from patients with acute nonlymphocytic leukemia (ANLL) and chronic myelogenous leukemia. Western blotting revealed that HL-60 progranulocytic leukemia cells contained an average of 0.1 x 10(6) copies of lamins A and C per cell compared to 0.5 x 10(6) copies of lamin B1 (the quantitatively prominent human B-type lamin) per cell. During the process of phorbol ester-induced maturation to macrophages, the mRNA for lamins A and C increased in abundance, with a concomitant 4-fold increase in the average cellular content of these polypeptides. To rule out the possibility that the low but detectable levels of lamins A and C observed in untreated HL-60 cells reflected incipient maturation, the content of lamins A and C was analyzed in ANLL cell lines that do not mature toward granulocytes or monocytes. Lamins A and C were readily detected in cell lines (KG1a, HEL, Mo-7e) derived from patients with a variety of subtypes of ANLL. Expression of lamins A and C was not limited to myeloid cell lines. These polypeptides were also detectable in marrow samples from 9 of 26 patients with ANLL including at least 1 patient from each of the 5 subtypes of ANLL examined. In contrast, only 1 of 12 marrow samples from patients with aggressive phase chronic myelogenous leukemia and chronic myelogenous leukemia in blast crisis contained readily detectable lamins A and C. The implications of these findings for current hypotheses regarding the functions of the lamin polypeptides are discussed.
Kaufmann
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Oncology Center, Johns Hopkins Hospital, Baltimore, Maryland 21205.
D001752:Blast Crisis / Q000378:metabolism; D001853:Bone Marrow / Q000737:chemistry; D006801:Humans; D034921:Lamin Type B; D034882:Lamins; D007942:Leukemia, Experimental / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000378:metabolism*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D014407:Tumor Cells, Cultured
D034921:Lamin Type B; D034882:Lamins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins