Clinicopathological aspects of therapy-related acute myeloid leukemia and myelodysplastic syndrome

Therapy-related myeloid neoplasm (t-MN) is a rare but devastating consequence of chemotherapy and/or radiotherapy used for the treatment of solid cancers and various hematologic malignancies. Our current understanding of the etiology is that hematopoietic clones that are contemporaneous with the primary cancer and resistant to the cytotoxic exposure have the potential to undergo selective expansion and transformation to t-MN. Consequently, a large proportion of cases are associated with adverse risk factors, resulting in limited effective treatment options. Despite the emergence of some therapies with promising activity in t-MN, most effects are short-lived and allogeneic stem cell transplantation remains the only curative option for eligible patients. This review summarizes the current literature on t-AML and t-MDS, with the aim of providing practical recommendations on the clinical evaluation and management of these conditions.     

人工合成成骨生长肽对辐射损伤小鼠造血功能的保护作用

目的　探讨人工合成成骨生长肽 (sOGP)对辐射损伤小鼠造血功能的保护作用 ,阐明其剂量 效应关系。方法　以 4 .0和 7.5Gy13 7Csγ射线照射小鼠为模型 ,采用皮下注射和肌肉注射 2种给药途径连续 8d给予sOGP ,剂量范围为 0 .0 39～ 6 4 0nmol/(kg·d) ,观察外周血象、骨髓有核细胞数、骨髓粒系造血祖细胞集落形成(CFU G)、骨髓细胞分类和骨髓切片组织学等的变化。结果　sOGP能加快受照小鼠外周血白细胞、骨髓有核细胞数的恢复 ,在一定的剂量范围内呈明显的剂量依赖性 ,并能刺激髓外造血 ;促进 (CFU G)形成作用显著高于重组人粒系集落刺激因子 (rhG CSF)约 2倍 ;骨髓病理学观察显示sOGP能加快受照小鼠骨髓造血组织损伤的恢复 ,刺激骨髓粒系增生。结论　sOGP可明显促进受照射小鼠造血功能的恢复 ,其机制可能是通过作用于早期造血阶段或 (及 )改善微环境进而促进造血。     

Intracranial Extramedullary Hematopoiesis in β-thalassemia Major

A case of β-thalassemia major with a huge mass of hernatopoictic tissuc firmly attached tothe dura mater was reported This is the first case reported in China.     

Abrogation of IL-3 Requirements and Stimulation of Hematopoietic Cell Proliferationin Vitroandin Vivoby Carboxylic Acids

ABSTRACT: Short-chain fatty acids, such as butyrate and propionate, induce fetal globin gene expression and are under clinical investigation in the β-hemoglobinopathies. Limitations of the short-chain fatty acids as therapeutics include their rapid metabolism and a tendency to induce cell growth arrest if administered for prolonged periods. In studies described here, the cellular effects of other inducers of fetal globin, phenoxyacetic acid and derivatives of short-chain fatty acids and cinnamic acids, were investigated in the human erythroid cell line K562, the IL-3 dependent multi-lineage cell line (32D), and in mice and primates. Several test compounds supported 32D cell proliferation despite a 50-fold depletion of IL-3, which resulted in growth arrest and apoptotic death in control cells. The degree of proliferation induced by certain test compounds was similar to the degree of proliferation induced by Erythropoietin and G-CSF in the cells. Eight of ten compounds induced γ globin mRNA in K562 cells. A 2.5 to 6-fold increase in reticulocytosis was observedin vivoin mice treated with two prototype compounds. Pharmacokinetic studies of three prototype compounds demonstrated millimolar plasma concentrations after single oral doses for many hours in primates. These findings identify orally bioavailable compounds which induce γ globin gene expression and hematopoietic cell proliferation through an activity which partially abrogates requirements for IL-3. Such compounds provide potential for oral therapeutics which stimulate proliferation of hematopoietic cells of multiple lineages, as well as inducing fetal globin.     

自体造血干细胞移植治疗恶性血液病

为探讨恶性血液病的有效治疗方法,应用自体骨髓移植(ABMT)38例,自体外周血造血干细胞移植(ABSCT)13例,自体外周血造血干细胞与自体骨髓联合移植15例。治疗白血病54例,恶性淋巴瘤11例,多发性骨髓瘤1例。外周血造血干细胞采用化疗加多抗甲素或C—CSF动员。移植物采用微波、阿克拉霉素净化处理。结果:两组动员方案均有良好动员效果。ABSCT组及联合移植组造血功能恢复比ABMT组快(P<0.05),合并症少。66例中,45例仍呈持续缓解(CCR),中位CCR时间32(5～98)个月,复发21例。3年无病生存率及复发率分别为68.5％及26.1％。结果表明:自体造血干细胞移植是根治恶性血液病的有效手段。ABSCT及联合移植具有造血功能恢复快,合并症少等优点。微波和阿克拉霉素体外净化移植物是一种简便、有效的净化方法。     

Role of the stromal microenvironment in regulation of bone-marrow hematopoiesis after administration of dipyridamole

I. P. Pavlov First Leningrad Medical Institute. Central Roentgeno-Radiological Research Institute, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 7, pp. 98–100, July, 1990.