Progress in Targeting the TGFβ Pathway

Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are

References

• 1.Valcarcel D, Verma A, Platzbecker U, et al. Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes. Blood. 2015;126:1669.
• 2.Suragani RN, Cawley SM, Li R, Wallner S, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014 Jun 19;123(25):3864-72.
• 3.Dussiot M, Maciel TT, Fricot A, et al. Nat Med. 2014 Apr;20(4):398-407.
• 4.

     

儿童MDS伴骨髓嗜酸细胞增多6例

骨髓增生异常综合征(MDS)伴骨髓嗜酸细胞增多(MDSEO),是MDS的特殊亚型,国外已有成人方面的报道[1],国内尚未见儿童MDSEO的系统介绍。1986年元月至 2000年12月,本科共诊断儿童 MDS 77例,其中 MDSEO6例,占 7.8%,现报道如下。     

Treatment of myelodysplastic syndromes with human granulocytic-macrophage colony stimulating factor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside.

In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM-CSF (3 micrograms/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14-d periods, interrupted by 14-d rest periods. Eight patients discontinued the treatment. In the GM-CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM-CSF plus AraC group but in none of the GM-CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM-CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3-month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM-CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM-CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM-CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases.     

骨髓增生异常综合征(附33例临床分析)

本文分析我院33例MDS病例的入院前诊断、病例类型、临床表现、血象及骨髓象资料,其中4例转变为急性白血病。     

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Mutation analysis in 16 patients with mtDNA depletion

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS.     

脑动脉瘤栓塞疗法完美实施的基础

目的：探索栓塞疗法治疗脑动脉瘤达到理想结果的条件。方法：１９９６年４月至２０００年４月间栓塞治疗３３例动脉瘤患者。以球囊栓塞４例,以机械解脱式钨丝弹簧圈栓塞２０例,以电解脱式铂金弹簧圈栓塞９例。结果：闭塞载瘤动脉４例,１００％闭塞８例,９５％闭塞１５例,９０％闭塞６例。无手术并发症。随访（门诊或信访）３３例无再出血。造影随访８例,其中术后１个月复查造影的２例均保持术后栓塞程度,术后３个月复查的３例     

骨髓增生异常综合征细胞形态学观察

目的：观察骨髓增生异常综合征(MDS)骨髓细胞形态学病态改变。方法：用瑞氏-姬姆萨混合染液染色，进行骨髓及外周血细胞学分析。结果：粒、红、巨核三系都有不同程度的病态造血。粒系主要以细胞核浆发育不平衡，内外浆、中性粒细胞核分叶不能或Pelger-Huet样畸形。结论：MDS三系均有不同程度的病态改变，患者以中老年居多，分型主要以RA为主。     

Early fulminant leukaemia post autologous bone marrow transplantation in non-hodgkin’s lymphoma patients

Although autologous bone marrow transplantation (ABMT) is a curative option for about 50% of the patients with progressive or relapsing Symphomas, considerable concern has been raised recently over the emerging rates of secondary malignancies following ABMT. A 15% cumulative incidence of myelodyspfasia 5 years after BMT is of major concern. We hereby describe a unique form of leukaemia occuring 4–6 weeks post ABMT for non-Hodgkin’s iymphoma patients. The possible etiology for this phenomenon as well as its relation to the classical MDS post ABMT is discussed.     

IL-15对儿童MDS造血前体细胞bcl-2、bcl-xl mRNA表达的影响

目的 探讨IL-15对骨髓增生异常综合征(MDS)造血细胞bcl-2、bcl—xl mRNA表达的影响，以探索IL-15抑制MDS CD34^ 造血干／祖细胞凋亡的可能机制：方法 采用吸附单克隆抗体的免疫磁珠分离系统，分离纯化17例MDS患儿骨髓CD34^ 细胞，采用RT—PCR检测bcl-2、bcl—xl mRNA表达水平，观察IL-15对它们的影响。结果 IL-15可呈时间与剂量依赖性的增强体外培养的MDS造血前体细胞bcl-2、bcl—xl基因mRNA的表达。结论 IL-15可能为抑制MDS CD34^ 造血干／祖细胞凋亡的作用机制之一。