Mazzella F M, Kowal-Vern A, Shrit M A, Rector J T, Cotelingam J D, Schumacher H R
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio, USA.
Mod Pathol. 2000 Apr;13(4):407-13. doi: 10.1038/modpathol.3880070.
Acute erythroleukemia is a relatively rare disorder of a multilineal nature. Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy. Forty-eight archival cases of acute erythroleukemia, subtypes M6a (the traditional FAB-M6), M6b (pure erythroleukemia), and M6c (>30% myeloblasts and >30% pronormoblasts by FAB exclusion criteria), were evaluated for multidrug resistance gene (MDR-1) status. Findings were correlated with clinical course and karyotypes. Immunohistochemical stain for the protein product of MDR-1, P-glycoprotein, was variably positive in 11 of 23 patients with M6a, as well as in all of the patients with M6b (strongly positive) and M6c (weakly positive). P-glycoprotein expression positively correlated with unfavorable cytogenetic aberrations, poor response to chemotherapeutic agents, and short survival. Most significant was that P-glycoprotein expression demonstrated a negative additive effect on response to treatment and prognosis with unfavorable cytogenetic anomalies. P-glycoprotein expression and multiple cytogenetic anomalies most probably contribute to the resistance to chemotherapy and poor survival characteristic of the patients with M6b (mean survival, 3.15 +/- 4.2 mo) and M6c (mean survival, 10.5 +/- 12.7 mo). Because patients with M6b and M6c have increased numbers of pronormoblasts in their bone marrow and past chemotherapeutic attempts have failed, chemotherapy directed at these cells is appropriate. Additional therapy directed toward the MDR-1 gene and its protein product seems indicated from our findings.
急性红白血病是一种相对罕见的多系性疾病。传统上，这类白血病患者接受标准的髓系治疗方案，M6a（其预后与急性髓系白血病相似）和M6b（尽管积极治疗但预后极差）的预后差异很大。对48例急性红白血病存档病例进行了评估，这些病例包括M6a（传统的FAB - M6）、M6b（纯红白血病）和M6c（根据FAB排除标准，原始粒细胞>30%且原红细胞>30%）亚型，检测其多药耐药基因（MDR - 1）状态。研究结果与临床病程和核型相关。MDR - 1蛋白产物P - 糖蛋白的免疫组化染色在23例M6a患者中有11例呈不同程度阳性，M6b患者（强阳性）和M6c患者（弱阳性）均呈阳性。P - 糖蛋白表达与不良细胞遗传学异常、对化疗药物反应不佳及生存期短呈正相关。最显著的是，P - 糖蛋白表达对伴有不良细胞遗传学异常的患者的治疗反应和预后具有负性累加效应。P - 糖蛋白表达和多种细胞遗传学异常很可能导致M6b患者（平均生存期3.15±4.2个月）和M6c患者（平均生存期10.5±12.7个月）化疗耐药和生存期短。由于M6b和M6c患者骨髓中原红细胞数量增加且既往化疗尝试失败，针对这些细胞的化疗是合适的。根据我们的研究结果，针对MDR - 1基因及其蛋白产物的额外治疗似乎是必要的。
