Vyas R C, Frankel S R, Agbor P, Miller W H, Warrell R P, Hittelman W N
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Blood. 1996 Jan 1;87(1):218-26.
The response of acute promyelocytic leukemia (APL) peripheral blood and bone marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during RA treatment using the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH). Before treatment, the predominant immature bone marrow cells were found to have t(15;17), whereas the residual mature granulocytes were diploid and lacked evidence of the translocation. In response to RA treatment, an increase in the leukocyte count was noted. The majority of these cells exhibited a t(15;17). Subsequently (eg, between days 6 and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The appearance of t(15;17) in gradually maturing elements suggests that RA contributed to a release of the maturation block of the leukemic elements. As responding patients obtained complete remission, diploid elements without evidence of the translocation prevailed in the blood and bone marrow. In 16 patients studied after 1 month in complete remission, all but 2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days later in 1 patient, whereas the second patient exhibited clinical evidence of relapse 20 days later. These results suggest that response of patients with APL to RA is associated with maturation, subsequent loss of the mature leukemic elements, and preferential regeneration of normal diploid hematopoietic elements.
在使用早熟染色体凝聚（PCC）和荧光原位杂交（FISH）技术的全反式维甲酸（RA）治疗期间，对急性早幼粒细胞白血病（APL）外周血和骨髓细胞对RA的反应进行了细胞遗传学特征分析。治疗前，发现主要的未成熟骨髓细胞存在t(15;17)，而残留的成熟粒细胞是二倍体，且没有易位的证据。对RA治疗的反应是白细胞计数增加。这些细胞中的大多数表现出t(15;17)。随后（例如，在第6天至23天之间），32%至91%的成熟髓系细胞仍表现出t(15;17)。在逐渐成熟的细胞成分中出现t(15;17)表明RA促成了白血病细胞成熟阻滞的解除。随着有反应的患者获得完全缓解，血液和骨髓中没有易位证据的二倍体细胞占主导。在完全缓解1个月后研究的16例患者中，除2例之外的所有患者均显示全部为二倍体细胞。1例患者残留的t(15;17)细胞在18天后消失，而另1例患者在20天后出现复发的临床证据。这些结果表明，APL患者对RA的反应与细胞成熟、随后成熟白血病细胞成分的消失以及正常二倍体造血成分的优先再生有关。
