棉酚对髓系白血病细胞凋亡的影响

目的:本实验拟通过棉酚对3种经典髓系白血病细胞系的研究,探索其治疗白血病的可能。方法:用细胞培养、四唑盐比色试验、形态学、DNA电泳等方法观察棉酚对白血病细胞的凋亡效应。结果:棉酚在浓度<6μmol/L时可选择地抑制白血病细胞的增殖、促进其凋亡,并表现出浓度依赖效应。结论:棉酚对髓系白血病细胞具有选择杀伤作用,表明其可能是一种高效低毒的抗白血病药物。     

Treatment and Survival in Patients with Chronic Myeloid Leukemia in a Chronic Phase in the West of Iran

Background: CML includes 30% of all leukemias, and occurs from childhood to old age. The present study was a retrospective analysis of chronic phase CML patients registered to a Hematology Clinic in Kermanshah, Iran, with checking of treatment options. Materials and Methods: Between 2002 and 2014, 85 CML patients referred to our hematology clinic were enrolled in our study. We surveyed age, sex, B-symptoms, splenomegaly, Sokal score, Hasford score, treatment and survival in all patients. Philadelphia chromosome analysis was conducted for each patient by conventional cytogenetics. We compared treatment in the patients with three drugs, imatinib, hydroxyurea (HU) and interferon alpha (IFN-α). Results: The mean age of the patients at diagnosis was 47.5±14.5 years (range, 23-82 years), with 43 (50.6%) being male. Some 13 (15.3%) were referred to our clinic for the first time with B-symptoms and 44 patients (51.8%) had splenomegaly. The Sokal score for 77 (90.6%) was low, 4 (4.7%) was intermediate and 4(4.7%) was high, but Hasford (Euro) scores for all patients were low. The 5-year survival rate for treated patients with imatinib, imatinib plus HU and imatinib plus HU plus IFN-α was 90.5%, 81.1% and 55.6%, respectively Conclusions: The results show that imatinib therapy alone provides better survival in CML patients compared to HU or IFN-α. Combinations of IFN-α and/or HU with imatinib probably reduce survival.     

Development of PH Positive Chronic Myeloid Leukemia in a Patient with Chronic Lymphocytic Leukemia Treated with Total Body Irradiation: A Rare Association

Philadelphia (ph) chromosome positive chronic myeloid leukemia developed in a patient treated for chronic lymphocytic leukemia after treatment with total body irradiation. The role of radiation in the development of CML is discussed.     

Chronic Lymphocytic Leukemia Associated with Myelodysplastic Syndrome and/or Chronic Myeloid Leukemia: Evidence for Independent Clonal Chromosomal Evolution

We describe the cytogenetic findings of three cases with simultaneous or sequential development of a B-chronic lymphocytic leukemia (B-CLL) and either a myelodysplastic syndrome (MDS) in 2 cases or a chronic myeloid leukemia (CML) in one case. The coexistence of these two hematologic malignancies leads to questions about their cell of origin. Through analysis of the cytogenetic abnormalities, we studied the derivation of both malignancies. The cytogenetic analyses of these three patients were simultaneously studied from both peripheral blood and bone marrow. Furthermore unstimulated short-time (USSTC) and long-time (72-96 hours) stimulated cultures (LTSC) were systematically performed. In all cases, we have demonstrated the independent bi-clonal evolution. This is the first report ever described for patients with CLPD and MDS and/or MPD shown to arise from distinct chromosomal abnormalities.     

7例格列卫联合非清髓造血干细胞移植治疗加速期、急变期CML的临床观察

目的探讨非清髓造血干细胞移植联合格列卫在治疗慢性粒细胞性白血病(CML)中的作用.方法7例CML患者(4例为AP,3例为BP),移植前、后口服格列卫(400～1 500mg/d)治疗,预处理方案为福达华氟达拉宾、环磷酰胺和阿糖胞苷联合ATG和(或)CD3单抗.供者HLA配型2例完全相合,2例一个位点不相合,1例3个位点不相合的同胞及2例半匹配的母亲供者,干细胞来源为G-CSF动员的外周血造血干细胞(PBSC),GVHD预防以环孢菌素A和骁悉为主,部分病例加用MTX、CD3单抗及CD25单抗(塞尼派).结果7例患者均获得不同程度的嵌合状态,3例获得完全嵌合(FC＞95%),4例获得44%～95%的混合嵌合,经调整免疫抑制剂、供者淋巴细胞/PBSC输注,格列卫治疗后,2例患者在移植后1.5～10个月转变为完全嵌合.移植后中性粒细胞＞0.5×109/L天数,16d(范围10～21d);血小板大于20×109/L天数,10d(范围4～15d).移植期间1例患者移植后45天因肠道感染,颅内出血死亡.另1例患者移植后27天因多脏器衰竭死亡.5例患者随访7～23个月,3例发生Ⅰ～ⅡGVHD,2例发生Ⅲ～ⅣGVHD,1例因cGVHD死于感染,余4例仍生存,平均无病生存12.2个月(7～17个月),Bcr/abl转阴时间33～130天,巡访期间无1例复发.结论非清髓造血干细胞移植前、后联合格列卫治疗CML,具有降低移植前白血病细胞负荷,抑制残留白血病细胞增殖,促进供者完全嵌合状态的转变,增强GVL效应的作用,是一种安全有效的治疗方法,值得进一步临床研究.     

慢性髓性白血病来源的树突状细胞诱导的CTL体外作用研究

 目的　研究慢性髓性白血病来源的树突状细胞的免疫功能。方法　分离慢性期CML患者外周血单个核细胞 (PBMNC) ,用细胞因子GM CSF及IL 4在体外诱导培养DC ,检测细胞表型 ,并观察其诱导的CTL体外抗肿瘤效应。用酶联免疫 (ELISA)方法测定CML DC混合淋巴细胞反应 (MLR)上清液中IL 12及IFN γ的量 ,并与正常DC进行比较。结果　联合GM CSF及IL 4可诱导CML细胞分化为CML DC ,CML DC的CD1a、CD80、CD83表达率均低于正常DC ;CML DC混合淋巴细胞反应上清IL 12及IFN γ含量均低于正常DC ;CML DC能诱导出对自身CML细胞有特异性杀伤作用的CTL。结论　CML DC具有抗原提呈细胞的免疫功能 ,能诱导抗白血病CTL反应。     

Overview of Chronic Myeloid Leukemia Patients in Pakistan in the Pre-Imatanib Era

Objectives: To study the patient characteristics of patients diagnosed with chronic myelogenous leukemia(CML) at a tertiary care cancer hospital in Pakistan. Methods and Materials: A retrospective analysis wasconducted on CML patients treated between 1996 and 2004 at Shaukat Khanum Memorial Cancer Hospital &Research Center. Results: A total of 461 CML patient charts were reviewed. The mean and median ages atpresentation were much younger than in the prior reports in the western literature with a quicker progressionof disease. Conclusion: The advent of tyrosine kinase inhibitors will likely have more impact on the lifespan ofCML patients in Pakistan when compared with patients in the western hemisphere due to younger age at diagnosis.     

High-dose Hydroxyurea and G-CSF to Collect Philadelphia-Negative Cells in Chronic Myeloid Leukemia: Preliminary Results

Five patients with Ph+ chronic myeloid leukemia and no detectable diploid cells in the marrow received 6 g hydroxyurea twice daily for 7 days followed by G-CSF to harvest Ph- cells 1-84 months after diagnosis. Three were in first chronic phase, and two in accelerated phase. One stopped hydroxyurea after 4 doses due to intractable vomiting and was not apheresed, while two stopped hydroxyurea after 9 and 11 doses because of mucositis and skin rash. Two tolerated all doses; one with no significant side effects, and one with mucositis and painful plantar rash. The nadir leukocyte, neutrophil, and platelet counts were 0.4-0.8, 0-0.1, and 2-19 × 10⁹/L respectively. Apheresis was commenced when the leukocytes were 1.2-3.8 × 10⁹/L 9-10 days after starting G-CSF, and 6 aphereses were performed. Four collections were 100% Ph+, and two 22% and 90% Ph-. The total nucleated cell, CD34+/CD34- subset, CD34+/CD33+ subset, and CFU-GM yields per kg per collection were 0.48-2.38 (median 1.18) × 10⁸, 0-0.48 (median 0.012) × 10⁶, 0.028-10.19 (median 0.92) × 10⁶, and 0.29-41.81 (median 21.78) × 10⁴ respectively. We conclude that hydroxyurea in the dose we used is poorly tolerated, and is associated with significant adverse effects including severe myelosuppression. It is possible to harvest diploid cells during recovery, but achievement of Ph-negativity appears to be erratic and cell yields are poor.     

Neuropilin-1某因在髓细胞白血病和正常人骨髓基质细胞中的表达(英文)

目的了解 neuropilin-1(NP-1)基因在髓细胞白血病(AML 和 CML)患者及正常人骨髓基质细胞中的表达情况。方法收集12例 AML、14例 CML 和20例正常对照骨髓标本,分离单个核细胞。进行体外长期培养,收集贴壁细胞(骨髓基质细胞)。利用逆转录-聚合酶链反应分别检测3组骨髓基质细胞中 NP-1基因的表达。结果成功建立了 AML、CML 和正常人骨髓基质细胞培养方法,NP-1基因在 AML、CML 骨髓基质细胞中的表达率分别为47.1%和50%,明显低于正常对照(85%)。结论 NP-1基因可表达于部分 AML、CML 和大部分正常人的骨髓基质细胞中,其在髓细胞白血病患者骨髓基质细胞中的低表达,可能与其调节造血功能异常有关。     

Neuropilin-1基因在髓细胞白血病和正常人骨髓基质细胞中的表达

目的了解neuropilin-1(NP-1)基因在髓细胞白血病(AML和CML)患者及正常人骨髓基质细胞中的表达情况。方法收集12例AML、14例CML和20例正常对照骨髓标本,分离单个核细胞。进行体外长期培养,收集贴壁细胞(骨髓基质细胞)。利用逆转录-聚合酶链反应分别检测3组骨髓基质细胞中NP-1基因的表达。结果成功建立了AML、CML和正常人骨髓基质细胞培养方法,NP-1基因在AML、CML骨髓基质细胞中的表达率分别为47.1%和50%,明显低于正常对照(85%)。结论NP-1基因可表达于部分AML、CML和大部分正常人的骨髓基质细胞中,其在髓细胞白血病患者骨髓基质细胞中的低表达, 可能与其调节造血功能异常有关。     

Expression of Cytokine mRNA in Leukemic Cells from Adult T Cell Leukemia Patients

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-lα (IL-l α ), IL-l β , IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and MTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-l α , IL-I β and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.     

更昔洛韦对慢性粒细胞白血病细胞生长和分化影响及其机制研究

目的：探讨更昔洛韦（ＧＣＶ）对人白血病细胞的抗增殖和诱导分化作用。方法：ＧＣＶ加入Ｋ５６２细胞培养４ｄ,测定其活细胞数目、克隆形成率、联苯胺染色阳性率,观察光镜形态、组织化学染色,并地行流式细胞分析、端粒酶检测。结果：在ＧＣＶ的作用下,Ｋ５６２细胞地增殖受抑,生长分数降低,并且向具有合成血红蛋白能力的细胞分化。结论：ＧＣＶ对Ｋ５６２细胞具有抑制增殖和诱导分化作用,该结果为慢性粒细胞白血病（ＣＭＬ）的治疗探索新的途径。