CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.
ADP-ribosyl Cyclase 1 ; antagonists & inhibitors ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; Humans ; Purines ; chemical synthesis ; chemistry

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.
Humans ; Multiple Myeloma/pathology* ; ADP-ribosyl Cyclase 1 ; Antibodies, Monoclonal/pharmacology* ; Hematologic Neoplasms/drug therapy*

OBJECTIVE: To investigate the apoptosis of CD34CD38-KG1a leukemia stem cells induced by Qinba selenium-mushroom extract(FA-2-b-β), and its related mechanism. METHODS: CD34CD38--KG1a cells were isolated from KG1a cell line by magnetic activated cell sorting. The proliferation ability of KG1a stem cells treatd by various concentration of FA-2-b-β(1.2-2.4 mg/ml) in vitro for 24 and 48 hours were tested by cell counting Kit-8(CCK8). Flow cytometry was used to detect the apoptosis rate of KG1a stem cells in each group after treated by FA-2-b-β in vitro. Expression of BAX,BCL-2,Casepase-3 and Cyclin D1 protein were detected by Western blot. RESULTS: The proportion of CD34CD38--KG1a stem cells was (95.35±2.63）% after immunomagnetic isolation. The proliferation of KG1a stem cells was inhibited significantly by FA-2-b-β, which shows a time- and dose-dependent manner (24 h,r=0.943; 48 h,r=0.976). Flow cytometry shows that with the increasing of drug concentration, the apoptosis was also increased, when KG1a stem cells was treated by FA-2-b-β for 24 h. Western blot indicated that the expression of apoptosis-related protein BAX and Casepase-3 were up-regulated, the expression of BCL-2 and Cyclin D1 were down-regulated. CONCLUSION FA-2-b-β can regulate proliferation and apoptosis KG1a stem cells, the involved mechanism may be related with the activation of mitochondrial-mediated apoptotic pathway.
ADP-ribosyl Cyclase 1 ; Antigens, CD34 ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Membrane Glycoproteins ; Neoplastic Stem Cells ; Selenium

OBJECTIVE: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH METHODS: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed. RESULTS: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34 CONCLUSION The percentage of CD34
ADP-ribosyl Cyclase 1 ; Antigens, CD34 ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; Neoplastic Stem Cells ; Prognosis ; Recurrence ; Remission Induction

OBJECTIVETo investigate the effects of Tpo and/or IL-11 gene modified stromal cells on the expansion of CD(34)(+) hematopoietic stem/progenitor cells in cord blood.

METHODSRetroviral vectors containing Tpo or IL-11 gene were constructed and used to transfect the stromal cell line HFCL. Tpo and/or IL-11 mRNA was assayed by Northern blot. Non-modified stromal cells were used, CD(34)(+) hematopoietic stem/progenitor cells from cord blood were expanded on gene-modified stromal cells for 7 days. The phenotype of CD(34)(+)CD(38)(-) primitive progenitors was detected by flow cytometry.

RESULTSHFCL expressed Tpo and/or IL-11 mRNA after transfected by the retroviral vectors. The percentages of CD(34)(+)CD(38)(-) primitive progenitors in the cultures of Tpo, IL-11 and Tpo + IL-11 modified HFCL were (1.8 +/- 0.24)%, (1.62 +/- 0.23)%, and (2.45 +/- 0.28)%, respectively, which were higher than that in the control [(0.8 +/- 0.23)%].

CONCLUSIONThe stromal cells modified by Tpo and/or IL-11 gene were able to enhance ex vivo expansion of CD(34)(+) and CD(34)(+)CD(38)(-) hematopoietic stem/progenitor cells from cord blood.

ADP-ribosyl Cyclase ; analysis ; ADP-ribosyl Cyclase 1 ; Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Fetal Blood ; cytology ; Hematopoietic Stem Cells ; physiology ; Humans ; Infant, Newborn ; Interleukin-11 ; genetics ; Membrane Glycoproteins ; Stromal Cells ; physiology ; Thrombopoietin ; genetics

To establish a basis for deep investigation of the role of microRNA (miRNA) in the regulation of hematopoiesis, differential expression profiles of miRNA between human cord blood CD34(+)CD38(-) and CD34(+)CD38(+) cells were analyzed. Mononuclear cells from cord blood (CB) of healthy donors were separated by Ficoll-Hypaque density gradients. CD34(+)CD38(-) and CD34(+)CD38(+) cells were sorted by using FACS Vantage SE. Their mRNA were then extracted and hybridized to miRNA microarray chip. The resulting data were analyzed with GeneSpring and informatics technique. The results showed that eleven miRNAs were found to be downregulated and 73 miRNAs to be upregulated by at least two-fold in the CD34(+)CD38(+) cells of CB, compared with the CD34(+)CD38(-) cells, which maintained CD34(+)CD38(-) cells' self-renewal and multiple lineage potential, that were defined as "stemness" miRNAs. 12 of the 84 genes (14.29%) were common to 33 hematopoietic-expressed miRNAs expressed by CD34(+) cells from both peripheral blood and bone marrow in Georgantas's study, which included 10 upregulated miRNAs (hsa-miR-23b, -26b, -92, -107, -130a, -181a, -197, -213, -222, -223) and 2 downregulated ones (hsa-miR-16a, -155). Some "stemness" miRNAs undergo CD34 antigen-like expression pattern during development and commmitted differeniation of hematopoietic stem cell/progenitors. Hematopoiesis-associated miRNA clusters and putative target genes could be found with informatics technique. It is concluded that the hematopoietic "stemness" miRNAs play important roles in normal hematopoiesis: miRNA expression profiles of hematopoietic stem cell/progenitors --> their gene expression profiles --> their self-renewal and lineage-commmitted differeniation.
ADP-ribosyl Cyclase 1 ; immunology ; Antigens, CD34 ; immunology ; Fetal Blood ; immunology ; metabolism ; Gene Expression Profiling ; Hematopoietic Stem Cells ; cytology ; immunology ; physiology ; Humans ; MicroRNAs ; genetics ; metabolism

The study was aimed to investigate the origination of abnormal clones in hematopoietic cells of MDS patients. That is to say if there are abnormal clones in CD34(+)CD38(-) and CD34(+)CD38(+) cells and their proportions in MDS patients. Immuno-magnetic bead technique was used to sort CD34(+)CD38(-) and CD34(+)CD38(+) in bone marrow mononuclear cells of 9 MDS patients with chromosome abnormalities (four cases with trisomy 8, 1 case with trisomy 8 complex karyotype, 2 cases with 5q(-), 1 case with 5q(-)complex karyotype, 1 case with 5q(-) accompanying trisomy 8) and smears were made respectively. Then the percentage of abnormal clones in CD34(+)CD38(-) and CD34(+)CD38(+) cells were compared by using FISH. The results indicated that abnormal clones were involved in the two population cells in 9 patients. The percentage of abnormal clones in CD34(+)CD38(-) cells (41.8 ± 8.4%)was obviously lower than that in CD34(+)CD38(+) cells(72.4 ± 7.7%) (p < 0.001), and the percentage of abnormal clones in karyocytes was 70.8 ± 9.2%. It is concluded the abnormal clones of bone marrow hematopoietic cells may originate from stem cell stage in MDS patients with 5q(-) and +8, and the abnormal clones are predominant at stage of progenitors.
ADP-ribosyl Cyclase 1 ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; Bone Marrow Cells ; cytology ; Chromosome Aberrations ; Clone Cells ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics

To cultivate CD34(+)CD38(-) cells isolated from umbilical cord blood of healthy puerperal women over a longer-period of time for observation of cell division, proliferation, apoptosis, and effects of stem cell factor on the growth of CD34(+)CD38(-) cells, with flow cytometry, CD34(+)CD38(-) cells were isolated from umbilical cord blood of 10 healthy puerperal women and cultivated in stem cell media with supplement of IL-3, IL-6, GM-CSF, EPO, IGF-1 and SCF 6 kinds cell growth stimulating factors for six months. The cell growth curves were established. The effects of stem cell factor on the growth of CD34(+)CD38(-) cells and cell apoptosis were investigated with the single cell gel electrophoresis technique and flow cytometry method, respectively. The results showed that CD34(+)CD38(-) cells isolated from umbilical cord blood were capable of proliferating after being cultivated in vitro over a longer-period of time with no evidence of the presence of excessive apoptosis. In conclusion, under appropriate culture conditions, CD34(+)CD38(-) hematopoietic early progenitor cells from umbilical cord blood can serve as a resource providing a large amount of primitive cells for transplantation therapy after a longer period of cultivation and proliferation in vitro.
ADP-ribosyl Cyclase 1 ; analysis ; Adult ; Antigens, CD34 ; analysis ; Apoptosis ; Cell Proliferation ; Cells, Cultured ; Female ; Fetal Blood ; cytology ; immunology ; Flow Cytometry ; Hematopoietic Stem Cells ; cytology ; immunology ; Humans

ADP-ribosyl Cyclase 1 ; immunology ; Biopsy ; Bone Marrow ; immunology ; pathology ; Epoxy Resins ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; immunology ; Plastic Embedding ; Staining and Labeling ; methods

OBJECTIVETo cultivate hematopoietic stem/progenitor cells (CD34(+)CD38(-)) isolated from umbilical cord blood (UCB) long for the observation of cell growth and expansion in vitro, surface marker expression, and chromosomal complements.

METHODSBy flow cytometry CD34-FITC and CD38-PE labeled CD34(+) and CD38(-) stem/progenitor cells were isolated from UCB. The cells were cultivated in vitro for 6 months in a stem cell culture system with addition of six kinds of cell growth factors (IL-3, IL-6, GM-CSF, Epo, SCF, IGF-1). One month after cultivation, cultured cells were investigated for surface marker expression by flow cytometry and karyotype by G banding method.

RESULTSAfter 7-12 days cultivation, the CD34(+)CD38(-) stem/progenitor cells began proliferation. The proliferation rate and the peak proliferation duration were greater in 1 cell/well cultivation conditions than in 10 cells/well. The cells remained CD34(+)CD38(-) and their karyotypic characteristics remained unchanged.

CONCLUSIONCD34(+)CD38(-) stem/progenitor cells from UCB may provide a larger than original amount of stem/progenitor cells for transplantation after long-term cultivation in vitro.

ADP-ribosyl Cyclase 1 ; immunology ; Adult ; Antigens, CD34 ; immunology ; Cell Proliferation ; Cells, Cultured ; Female ; Fetal Blood ; cytology ; immunology ; Hematopoietic Stem Cells ; cytology ; immunology ; Humans ; Immunophenotyping ; Karyotyping