急性早幼粒细胞白血病合并骨髓纤维化及与TGF-β_1的关系

Acute Promyelocytic Leukemia with Marked Myelofibrosis: Possible Involvement of TGF-β_1

目的:我们报道了一例急性早幼粒细胞白血病合并骨髓纤维化患者,并对转化生长因子-β(TGF-β_1)与骨髓纤维化的关系作初步探讨。方法:我们应用骨髓细胞学、骨髓活检、骨髓染色体核型分析、流式细胞仪检测细胞免疫表型、实时定量PCR检测PML/RARαmRNA表达对该患者进行诊断。同时观察合并MF对该患者疗效的影响。然后于该患者初诊时及缓解后,分别用ELISA法检测血清TGF-β_1,用RT-PCR检测细胞中TGF-β_1基因的表达,5例未合并骨髓纤维化的急性早幼粒细胞白血病患者作为对照组。结果:该患者的特点为:合并明显骨髓纤维化,白血病细胞胞浆内无颗粒或含微小颗粒,形态学符合M3v,另外白血病细胞高表达干细胞表型CD34及HLADR,PML/RARα融合基因亚型为S型。该患者合并骨髓纤维化与疗效无关。该患者初诊时血清中TGF-β_1及细胞中TGF-β_1基因的表达均明显高于缓解后及对照组。结论:该患者合并骨髓纤维化是早幼粒细胞白血病的罕见类型,骨髓纤维化的发生可能为CD34^+的白血病细胞高表达TGF-β_1基因所致。

Objective：We report here an acute promyelocytic leukemia with marked myelofibrosis（MF）, and investigate the possible involvement of TGF-β1.Methods：The case is diagnosed by marrow aspirate and biopsy, immunophenotyping study using flow cytometry, chromosomal analysis, PML/RARα mRNA detected by real-time PCR. The effect of MF on prognosis in the patient is assessed. The serum concentration of TGF-β1 is dected by ELISA, TGF-β1 mRNA in APL cells are dected by RT-PCR at diognosis and after the second course of consolidation chemotherapy respectively. The control group consist of 5 cases with acute promyelocytic leukemia without MF. Results：This patient is a variant form（M3v） of acute promyelocytic leukemia with atypical morphologic features, immature antigens（CD34 and HLA-DR）, marked MF, the PML/RARα. hybrid gene is S style.The complete recovery of this patient is not delayed, serum concentration of TGF-β1 and TGF-β1 mRNA in APL cells was much higher than the control group at dignosis, decreasing after resolution of MF.Conelusion： Tiffs patient is a rare case with acute promyelocytic leukemia presenting as MF.It is possible that TGF-β1 released from APL cells expressing CD34 antigen may have been involved in the development ef MF in our patient.