Wu Hx

MiR-15a, miR-16-1 and miR-17-92 cluster expression are linked to poor prognosis in multiple myeloma.

Multiple myeloma (MM) is characterized by a profound genomic instability of potential prognostic relevance. Loss of chromosome 13, observed in almost half of patients, negatively affects prognosis. MiR-15a, miR16-1 and miR-17-92 cluster, located on 13q, play important roles in the regulation of cell proliferation, differentiation and apoptosis. Therefore, we investigated a possible correlation of miRNA expression with chromosome 13 deletions (del(13)) and prognosis. We measured the expression of miR-15a, miR16-1 in 70 newly diagnosed MM patients and miR-17-92 cluster in 85 newly diagnosed MM patients by quantitative real-time PCR analyses. MiR-15a, miR-16-1 and miR-17-92 cluster expression levels are independent of the del(13). High levels of miR-15a, miR-16-1, miR-17, miR-20a and miR-92-1 are associated with shorter progression-free survival (PFS), suggesting poor prognosis. Our data suggest that the expression of specific miRNAs may be contributing to MM prognosis.

Cotransplantation of HLA-identical mesenchymal stem cells and hematopoietic stem cells in Chinese patients with hematologic diseases

Mesenchymal stem cells (MSCs) may be employed to support hematopoietic reconstitution and mitigate graft‐vs.‐host disease (GVHD) in transplantation of hematopoietic stem cells (HSCs). The aim of this study was to explore the feasibility and safety of cotransplantation culture‐expanded MSCs and HSCs from the same human leukocyte antigen (HLA)‐identical sibling donor in Chinese patients with hematologic diseases. Bone marrow mononuclear cells from healthy donors were cultured and expanded ex vivo. Immunophenotype, adipogenic and osteogenic differentiation potential, and karyotype of the harvested MSCs were detected on those who had been cotransplanted with HSCs and MSCs from the same donor. Hematopoietic reconstitutions, complications, and clinical outcomes were observed after cotransplantation in these patients. (1.77 ± 0.40) × 106/kg (donor’s weight) MSCs were successfully expanded from 23.6 ± 5.96 ml of bone marrow samples. They had normal karyotypes with bi‐lineages differentiation potential, and were CD73, CD90, and CD105 positive. Twelve patients underwent cotransplantation with no observable adverse response during and after the infusion of MSCs. Hematopoietic reconstitutions were rapid. Two patients developed grade II–IV acute GVHD, and two extensive chronic GVHD. Four patients suffered from cytomegalovirus infection but were cured eventually. Up to now, seven patients have been followed as long as 29–57 months and five patients died. It is concluded that MSCs can be expanded effectively by culture and it is safe and feasible to cotransplant patients with allogenic culture‐expanded MSCs and HSCs.

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients.

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR=1.48, 95% CI: 1.08-2.02, Pc=0.03; GT: OR=1.96, 95% CI: 1.25-3.07, Pc<0.01), while genotype AT in this locus seemed to be protective (OR=0.29, 95% CI: 0.02-0.72, Pc=0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR=2.38, 95% CI: 1.52-3.74, Pc<0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR=5.21, 95% CI: 2.58-10.54, Pc<0.01); haplotype of G-T in 2677-3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR=3.97, 95% CI: 2.31-6.85, Pc<0.01; 2677GT/3435TT: OR=4.55, 95% CI: 2.02-10.22, Pc<0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677-3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.

The chromosomal translocation (11;14) (p13; q11) in acute B-Cell lymphocytic leukemia.

Background: Cytogenetic abnormalities are the most important independent prognostic factors of acute leukemia and imply the potential molecular mechanism of the disease. Translocation (11;14)(p13;q11) has been predominantly found in T-cell acute lymphocytic leukemia (ALL) but is rare in B-cell ALL. Case Report: We present the case of a 30-year-old male patient, who presented with symptomatic anemia, thrombocytopenia and leukocytosis. Bone marrow aspirate smear showed hypercellularity with 90.4% of blast cells, which were negative for peroxidase reaction and partially positive for periodic acid-Schiff reaction. Immunophenotyping analysis was positive for CD34, HLA-DR, CD13, CD33, CD19, CD22, cCD79c, and negative for CD2, CD3, CD7, CD8, CD10, CD20, cCD3. Conventional cytogenetic study by R-banding showed complex chromosome aberrations involving t(11;14)(p13;q11) with the following karyotype: 46,XY,t (11;14)(p13;q11)[2]/46,idem,add2(q?)[2]/46,XY,add16(p?) [3]/46,XY[13]. Fluorescence in situ hybridization analysis indicated the translocation of chromosomes 11 and 14, and was negative for BCR/ABL fusion. The patient went into complete remission after the first induction chemotherapy (ALL-IC-BFM 2002 regimen), but he relapsed and died after 4 months. Conclusions: Translocation (11;14) (p13;q11) in B-cell ALL is rare, but it is worth exploring the molecular mechanisms and discovering the prognostic value in more B-cell ALL patients.

MDR1 polymorphisms affect the outcome of Chinese multiple myeloma patients

OBJECTIVE To illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population. METHODS A total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS. RESULTS MDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061-0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264-0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms. CONCLUSION MDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.

Clinical analysis of 81 cases of malignant lymphoma treated with autologous hematopoietic stem cell transplantation

OBJECTIVE To investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma. METHODS The clinical data of 81 patients with malignant lymphoma received ASCT from April 1999 to October 2013 were retrospectively analyzed. Of 81 patients, 70 were non-Hodgkins lymphoma (NHL) and 11 Hodgkins lymphoma (HL). High dose of etoposide combined with G-CSF was used to mobilize peripheral hematopoietic stem cell. Preconditioning regimen was BEAM (carmustine + cytarabine + etoposide + melphalan). RESULTS Enough peripheral blood stem cells were collected from all patients. All of the patients after transplantation achieved hematopoietic reconstitution, the median time of the absolute neutrophil count (ANC) recovery to >0.5×10⁹/L time was 10(7-16) d, and the median time of platelet count recovery to >20×10⁹/L was 10(6-17) d. With the follow-up of 23(2-139) months, progression free survival (PFS) was 72.7%, and overall survival (OS) was 88.6%. The median PFS and OS were not reached. Complete remission (CR) before ASCT was an independent prognostic factor of PFS. No transplant related death happened. CONCLUSION ASCT was a safe and effective method for treatment of malignant lymphoma.