Seale J, Delva L, Renesto P, Balitrand N, Dombret H, Scrobohaci M L, Degos L, Paul P, Chomienne C
Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint Louis, Paris, France.
Leukemia. 1996 Jan;10(1):95-101.
The cells from patients with acute promyelocytic leukemia (AML M3) undergo terminal differentiation when treated with all-trans retinoic acid (ATRA). We have analyzed the expression of the mRNA for cathepsin G, a promyelocyte stage-specific transcript, in the leukemia and in retinoic acid responsive cell lines. We showed that the transcript is perpetually synthesized in patients' cells and that it rapidly disappears when the cells are treated with ATRA. In ATRA-sensitive (HL-60, NB4) cell lines and an ATRA-resistant (HL-60R) cell line we have shown that this process is dependent on proteins synthesized during the first 6h of ATRA-triggered differentiation and may involve both pre- and post-transcriptional mechanisms. A corresponding decrease in cathepsin G protein synthesis then follows. These findings indicate that the maturation arrest in AML M3 results in cells that may constitutively continue to produce proteins whose production is temporally confined during normal hemopoiesis. This would explain the elevated plasma-free serine protease activity we have demonstrated in this disease, and has implications for both the coagulopathy and the 'retinoic acid syndrome' in AML M3.
急性早幼粒细胞白血病（AML M3）患者的细胞在用全反式维甲酸（ATRA）治疗时会发生终末分化。我们分析了组织蛋白酶G（一种早幼粒细胞阶段特异性转录本）的mRNA在白血病及维甲酸反应性细胞系中的表达情况。我们发现，该转录本在患者细胞中持续合成，而在用ATRA处理细胞时会迅速消失。在对ATRA敏感的（HL-60、NB4）细胞系及对ATRA耐药的（HL-60R）细胞系中，我们发现这一过程依赖于ATRA触发分化的最初6小时内合成的蛋白质，且可能涉及转录前和转录后机制。随后组织蛋白酶G的蛋白质合成相应减少。这些发现表明，AML M3中的成熟停滞导致细胞可能持续组成性地产生在正常造血过程中其产生受时间限制的蛋白质。这可以解释我们在该疾病中所证明的血浆游离丝氨酸蛋白酶活性升高，并对AML M3中的凝血病和“维甲酸综合征”都有影响。
