Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy
Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy
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DOI：
10.3324/haematol.2011.044933
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发表时间：
2011-10-01
期刊：
影响因子：
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通讯作者：
Sanz, Miguel A.
中科院分区：
文献类型：
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作者：
Barragan, Eva;Montesinos, Pau;Sanz, Miguel A.
BackgroundFms样酪氨酸激酶-3（FLT 3）基因突变是常见的急性早幼粒细胞白血病，但其预后价值还没有很好地建立.Design and MethodsWe评估了FLT 3-内部串联重复和FLT 3-D835突变的患者治疗全反式维甲酸和蒽环类药物为基础的化疗登记在两个随后的试验中的研究和治疗出血性白血病（PETHEMA）结果FLT 3-内部串联重复和FLT 3-D835突变分别为306例（41%）和213例（29%）。分别有68例（22%）和20例（9%）患者存在内部串联重复和D835突变。内部串联重复与较高的白色血细胞和原始细胞计数、乳酸脱氢酶、复发风险评分、发热、出血、凝血病、BCR 3亚型、M3变异亚型以及CD 2、CD 34、人类白细胞抗原DR和CD 11 b表面抗原的表达相关。FLT 3-D835突变与任何临床或生物学特征均无显著相关性。单变量分析显示，FLT 3-内部串联重复的患者复发率较高，生存率较低，而FLT 3-D835未观察到影响。结论FLT 3-内部串联重复突变与急性早幼粒细胞白血病的一些血液学特征相关，尤其是与高白色细胞计数相关，但我们无法证明FLT 3-内部串联重复突变在全反式维甲酸和蒽环类药物治疗的急性早幼粒细胞白血病患者中的独立预后价值。
BackgroundFms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established.Design and MethodsWe evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005.ResultsFLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis.ConclusionsFLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.