Wnt Signaling In Hematopoietic Stem Cell Aging

Purpose: To analyze gene expression changes of components of the Wnt signaling pathwayin aging hematopoietic stem cells.Methods: Use ordinary PCR, real time PCR and western blot to analyze Wnt componentsexpression in bone marrow cells and hematopoietic stem cells isolated from TERC-/- mice(telomerase-deficient mice null for the telomerase RNA component)and wide type mice bymagnetic bead sorting (MACS) and fluorescence activated cell sorting (FACS).Results: Wnt5b transcripts were significantly upregulated in total bone marrow cells ofTERC -/- mice, while Fzdl and Lefl transcripts were significantly downregulated in totalbone marrow cells as well as hematopoietic stem cells of TERC -/- mice. Lefl was alsodownregulated at protein level in total bone marrow of TERC -/- mice.Conclusion: The canonical Wnt signaling pathway was downregulated in total bonemarrow cells as well as in hematopoietic stem cells of TERC -/- mice, while thenoncanonical Wnt signaling pathway was upregulated in total bone marrow cells in TERC-/- mice, which might contribute to the impaired regenaration ability of stem cells of theaccelerated aging mice. Objective: To explore the effects of cotransplantation of hematopoietic stem cells (HSC)and stromal cells derived from aorta-gonad-mesonephros (AGM) region on hematopoieticreconstitution in mice after bone marrow transplantation.Methods: The typical model of syngeneic BMT was established and the model mice wererandomly divided into 3 groups: the control group, the BMT group, and the group ofcotransplantation of HSC with AGM stromal cells (the cotransplantation group). Thefollowing factors were measured on day 7, 10, 14, 21 and 28 after BMT: peripheral whiteblood cells(WBC) and platelets(PLT), bone marrow mononuclear cells (BMMNC), andhistology changes of bone marrow.Results: The levels of peripheral WBC, PLT and BMMNC in the contransplantation groupwere higher than those of the single BMT group and the control group.Conclusion: Cotransplantation with AGM stromal cells could significantly promotehematopoietic reconstruction in mice after BMT. Cotransplantation may represent apromising means of achieving higher engraftment rate after BMT. Purpose: This study moves towards this goal in understanding the significance ofcombined therapy of arsenic trioxide (As₂O₃) and all-trans retinoic acid (ATRA) in acutepromyelocytic leukemia (APL).Methods: Retrospective study of 80 APL patients was performed and the completeremission (CR), the recovery of the hemogram, the early mortality, and the adverse effectrates were analyzed between the ATRA group and the combined group.Results: CR rates of the two groups were 91.7% and 88.2% respectively, which showsno significant difference; time of reaching CR, hemoglobin recovery, and platelet recoveryfor the combined group were (28±7.8)days, (22.36±8.72)days and (19.38±9.52) daysrespectively, while those were (47.7±10.9) days,(28.40±8.95) days and (28.03±7.29) daysfor the ATRA group, which suggested a significantly shorter period of the combined groupof achieving recovery. With 11.1% compared to 20.8%, the mortality of the combinedgroup seemed lower than that of the ATRA group but no significance was observed. Theadverse effect rates of the two groups also lacked of significant difference.Conclusions: Compared to using ATRA alone, combined therapy of As₂O₃ and ATRAwas dominant in achieving CR and recovery for APL. Besides, the combined therapycarries the promise of reducing the early mortality with no aggravation of the adverseeffects.