Dubois C, Schlageter M H, de Gentile A, Guidez F, Balitrand N, Toubert M E, Krawice I, Fenaux P, Castaigne S, Najean Y
Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint Louis, Paris, France.
Blood. 1994 Jun 1;83(11):3264-70.
Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all-trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.
急性早幼粒细胞白血病（APL）是急性髓系白血病（AML）的一个同质性亚组，其特征为存在t(15;17)易位以及由此产生的早幼粒细胞白血病/维甲酸受体α（PML/RARα）融合蛋白。迄今为止，APL是唯一对全反式维甲酸（ATRA）的分化作用足够敏感的AML。在体内，单独使用ATRA可使大多数APL患者实现完全缓解。然而，仍观察到有治疗失败或部分缓解的情况，且尚未确定这些患者对ATRA无反应的分子基础。为深入了解APL细胞的生长和分化，对16例APL样本中白血病细胞所产生的造血生长因子（HGF）（白细胞介素-1β [IL-1β]、IL-6、肿瘤坏死因子α [TNFα]、粒细胞集落刺激因子 [G-CSF]、粒细胞-巨噬细胞集落刺激因子 [GM-CSF] 和IL-3）的表达进行了研究。12例APL病例表达IL-1β、IL-6和TNFα，但不表达G-CSF、GM-CSF和IL-3。这些病例通过ATRA治疗实现了完全缓解。其余4例患者（TNFα阴性或G-CSF、GM-CSF或IL-3阳性）未通过ATRA实现完全缓解。在所有病例中，体内对ATRA治疗的反应与10⁻⁶ mol/L全反式维甲酸的体外分化作用相关。因此，ATRA分化诱导与HGF表达密切相关（P <.0001）。这些结果表明，APL细胞中HGF表达的有无可能有助于ATRA对该疾病的治疗效果。
