Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet, and Hematology Center Karolinska, M54, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Med Oncol. 2012 Sep;29(3):2070-6. doi: 10.1007/s12032-011-0044-4. Epub 2011 Aug 23.
P-glycoprotein (PGP) over-expression on malignant cells is associated with poor prognosis and treatment outcome due to the development of a multidrug resistance phenotype. In this study, we analyzed the correlation between expression of PGP and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16-75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and who received at least one induction chemotherapy course, were enrolled in the study. Expression of PGP on ≥ 10% of the myeloblasts (PGP(+)AML) at the time of diagnosis was observed in 21 patients (41%). The complete remission rate did not differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of the 51 patients (24%) were still alive after a median follow-up time of 11.5 years (range 10.7-13.1). The Ly(+)AML patients showed significantly better overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at the last follow-up, P = 0.003). The subgroup of patients with co-expression of PGP and Ly also showed better overall survival compared with PGP(+)AML patients without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P = 0.04). Our results suggest that expression of lymphoid antigens on PGP(+) myeloblasts in AML can positively affect survival in AML patients, mainly due to a decreased relapse risk and better survival. Although the small number of patient may be perceived as a limitation of the study, the long follow-up period strengthens its value. Further prospective trials are needed to obtain more information concerning the association between PGP and lymphoid antigens in AML, which would put our results in their ultimate proper context.
多药耐药蛋白(PGP)在恶性细胞中的过度表达与不良预后和治疗结果相关,因为它会导致多药耐药表型的产生。在这项研究中,我们分析了白血病原始细胞上 PGP 的表达与淋巴细胞抗原(Ly)之间的相关性,以及它们与急性髓细胞白血病(AML)治疗反应和生存之间的关系。
51 例连续患者,年龄 16-75 岁(中位年龄 44.6 岁),1997 年至 2000 年间诊断为初发 AML,至少接受过一个诱导化疗疗程,纳入本研究。在诊断时,≥10%的原始细胞表达 PGP(PGP(+)AML)的患者有 21 例(41%)。PGP(+)(13/21)和 PGP(-)(20/30)患者的完全缓解率没有差异(62%比 67%)。在中位随访时间为 11.5 年(范围 10.7-13.1 年)后,51 例患者中有 12 例(24%)仍然存活。Ly(+)AML 患者的总生存明显优于 Ly(-)AML 患者(8/18 例与 4/33 例患者在最后一次随访时存活,P = 0.003)。PGP 和 Ly 共表达的患者亚组的总生存也明显优于 PGP(+)AML 患者无 Ly 表达(4/8 例与 0/13 例患者在最后一次随访时存活;P = 0.04)。
我们的结果表明,AML 中 PGP(+)原始细胞上淋巴细胞抗原的表达可以对 AML 患者的生存产生积极影响,主要是因为复发风险降低和生存改善。尽管患者数量较少可能被认为是该研究的一个局限性,但长期随访期增强了其价值。需要进一步的前瞻性试验来获得更多关于 AML 中 PGP 和淋巴细胞抗原之间关联的信息,这将使我们的结果处于其最终的适当背景中。