Latest Umbilical Blood Research

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Gene expression profiling of CD3gamma, delta, epsilon, and zeta chains in CD4(+) and CD8(+) T cells from human umbilical cord blood.
Primary Author: Shaohua Chen
Primary Author: Institute of Hematology, Medical College, Jinan University, Guangzhou, China.
Date Published: 2010 07 30
Abstract: In order to elucidate the feature of T-cell immune status in umbilical cord blood (CB) from humans, the expression levels of CD3gamma, delta, epsilon, and zeta chain genes in CD4(+) and CD8(+) T cells of CB were analysed by real-time PCR. CD4(+) and CD8(+) T cells sorted from 12 cases of CB and 10 peripheral blood (PB) samples from healthy adults were used in the study. The beta2-microglobulin gene was used as an endogenous reference, and the evaluations of mRNA expression level of each CD3 gene were used by the 2(-DeltaC(t)) x 100% method. In CD4(+) T cells, the expression levels of CD3gamma, delta, and zeta genes (16.54+/-6.49, 3.53+/-1.15, and 5.48+/-1.10%) from CB were significantly higher than those from PB (P=0.001, P=0.017, and P=0.000, respectively). Higher expression levels of CD3delta and zeta genes (3.43+/-1.19 and 5.24+/-1.42%) in CD8(+) T cells from CB were found than those from PB (P=0.000 and P=0.004). Moreover, the expression level of CD3epsilon gene in CD4(+) T cells from CB (13.29+/-5.72%) was significantly different from that in CD8(+) T cells (7.81+/-4.72%, P=0.018). Thus, the expression pattern of four CD3 genes were gamma>epsilon>zeta>delta in both CD4(+) and CD8(+) T cells from CB, while similar expression pattern was found in CD8(+) T cells from PB samples. In contrast, the expression pattern was presented as epsilon>gamma>zeta>delta in CD4(+) T cells from PB. In conclusion, the present study characterized the expression pattern of CD3gamma, delta, epsilon, and zeta chain genes in CD4(+) and CD8(+) T cells from CB, which might be very useful for further understanding the feature of T-cell immune status in umbilical cord blood. Higher expression of CD3 genes in CD4(+) T cells might relate to the strong ability of activation of TCR-mediated signals, and suggests that this is one of the features responsible for the low allo-reactivity of CB T cells.

Influence of glutathione S-transferase A1, P1, M1, T1 polymorphisms on oral busulfan pharmacokinetics in children with congenital hemoglobinopathies undergoing hematopoietic stem cell transplantation.
Primary Author: Ronit Elhasid
Primary Author: Pediatric Hemato-Oncology and Bone Marrow Transplant Department, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
Date Published: 2010 7 30
Abstract: BACKGROUND: Busulfan (BU), often used in high dose for myeloablation before hematopoietic stem cell transplantation (HSCT), has been implicated in certain HSCT toxicities, including the occurrence of hepatic veno-occlusive disease (HVOD). In addition to weight and age, gene polymorphisms in specific members of the glutathione-transferase (GST) gene family (A1, P1, M1, and T1), involved in BU metabolism, may play a role in the wide inter-patient variability in systemic BU concentrations. PROCEDURE: The present study integrated clinical data regarding the occurrence of HVOD, graft versus host disease (GVHD), BU pharmacokinetics and GSTA1, GSTP1, GSTM1, and GSTT1 genotypes of 18 children who received BU in their pre-HSCT conditioning regimen. The children were all treated for congenital hemoglobinopathies and were all of Arab Moslem descent. RESULTS: The data demonstrate an association between GSTA1 and GSTP1 genotypes and BU-maximal concentration (C(max)) (P = 0.01, P = 0.02, respectively), area under the concentration-time curve (AUC) (P = 0.02, P = 0.01, respectively) and oral BU clearance/kg body weight (P < 0.02, P = 0.08, respectively). GSTM1-null individuals demonstrated lower BU-AUC/Kg compared to GSTM1-positive individuals. In addition, an association between GVHD and GSTM1-null genotype was found. CONCLUSIONS: GSTA1, GSTP1, and GSTM1 genotyping prior to HSCT in children with congenital hemoglobinopathies may allow better prediction of oral BU kinetics and the need for BU dose adjustment, as well as prediction of transplant related toxicity such as GVHD, thereby improving clinical outcome. Pediatr Blood Cancer. (c) 2010 Wiley-Liss, Inc.

Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study.
Primary Author: Marcos de Lima
Primary Author: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Date Published: 2010 7 30
Abstract: BACKGROUND:: Recurrence is a major cause of treatment failure after allogeneic transplantation for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and treatment options are very limited. Azacitidine is a DNA methyltransferase inhibitor with activity in myeloid disease. The authors hypothesized that low-dose azacitidine administered after transplant would reduce recurrence rates, and conducted a study to determine a safe dose/schedule combination. METHODS:: Forty-five high-risk patients were treated. Median age was 60 years; median number of comorbidities was 3; 67% were not in remission. By using a Bayesian adaptive method to determine the best dose/schedule combination based on time to toxicity, the authors investigated combinations of 5 daily azacitidine doses, 8, 16, 24, 32, and 40 mg/m(2), and 4 schedules: 1, 2, 3, or 4 cycles, each with 5 days of drug and 25 days of rest. Cycle 1 started on Day +40. RESULTS:: Reversible thrombocytopenia was the dose-limiting toxicity. The optimal combination was 32 mg/m(2) given for 4 cycles. Median follow-up was 20.5 months. One-year event-free and overall survival were 58% and 77%, justifying further studies to estimate long-term clinical benefit. No dose significantly affected DNA global methylation. CONCLUSIONS:: Azacitidine at 32 mg/m(2) given for 5 days is safe and can be administered after allogeneic transplant for at least 4 cycles to heavily pretreated AML/MDS patients. The trial also suggested that this treatment may prolong event-free and overall survival, and that more cycles may be associated with greater benefit. Cancer 2010. (c) 2010 American Cancer Society.