Nudt15-mediated inflammatory signaling contributes to divergent outcomes in leukemogenesis and hematopoiesis.

NUDT15 encodes nucleotide triphosphate diphosphatase that is responsible for metabolizing purine analog drugs, and its genetic mutation results in severe side effects from thiopurine therapy. However, the functions of Nudt15 in leukemic stem cells (LSCs) and hematopoietic stem cells (HSCs) remain unknown. Here we reveal the Nudt15-regulating self-renewal of both mouse LSCs and HSCs. Our data show that Nudt15 negatively regulates murine leukemogenesis and its deficiency prolongs the survival of murine AML recipients by impairing LSC self-renewal, while Nudt15 ablation markedly enhances mouse HSC regenerative potential and self-renewal. Mechanistically, Nudt15 modulates inflammatory signaling in mouse LSCs and HSCs, leading to divergent self-renewal outcomes. Nudt15 depletion inhibits mouse LSC self-renewal by downregulating Ifi30, resulting in elevating intracellular ROS level. Gata2, a key regulator, is required for Nudt15-mediating inflammatory signaling in mouse HSCs. Collectively, our results present new crucial roles of Nudt15 in maintaining the functions of mouse LSC and HSC through inflammatory signaling and have a new insight into clinical implications.

miR-30e-5p regulates leukemia stem cell self-renewal through the Cyb561/ROS signaling pathway.

Leukemia stem cells (LSC) represent a crucial and rare subset of cells present in acute myeloid leukemia (AML); they play a pivotal role in the initiation, maintenance, and relapse of this disease. Targeting LSC holds great promise for preventing AML relapse and improving long-term outcomes. However the precise molecular mechanisms governing LSC self-renewal are still poorly understood. Here, we present compelling evidence that the expression of miR-30e-5p, a potential tumor-suppressive microRNA, is significantly lower in AML samples than in healthy bone marrow samples. Forced expression of miR- 30e effectively inhibits leukemogenesis, impairs LSC self-renewal, and delays leukemia progression. Mechanistically, Cyb561 acts as a direct target of miR-30e-5p in LSC, and its deficiency restricts the self-renewal of LSC by activating reactive oxygen series signaling and markedly prolongs recipients' survival. Moreover, genetic or pharmacological overexpression of miR-30e-5p or knockdown of Cyb561 suppresses the growth of human AML cells. In conclusion, our findings establish the crucial role of the miR-30e-5p/Cyb561/ROS axis in finely regulating LSC self-renewal, highlighting Cyb561 as a potential therapeutic target for LSC-directed therapies.

[Clinical significance of measuring hepatitis B virus large surface protein in serum].

OBJECTIVE: To explore the significance of serum hepatitis B virus large protein( HBV-LP), HBV-DNA and markers of hepatitis B virus (HBV-M)in the diagnosis of viral replication. METHODS: Serum HBV-DNA level was quantitatively detected using PCR Real-time polymerase chain reaction, HBV-LP was detected by enzyme-linked immunosorbent assay (ELISA) and HBV markers expression were measured by chemiluminescence immunoassay method in 1886 cases of seurm. RESULTS: The results of hepatitis virus large protein (HBV-LP) detection and the detection results of HBV-DNA was no significant difference (chi2 = 1.142, P > 0.05). HBV-DNA logarithm of copies and A vaule of HBV-LP was a positive correlation (r = 0.487, P < 0.01). HBV-DNA copies of different groups was significantly different from HBV-LP A values (F = 7.772, P < 0.01). The results of HBV-LP and HBV-DNA detected in different patterns of HBV-M were not significantly different. In 36 healthy people,the detecting results of HBV-DNA and HBV-LP are negative. CONCLUSION: There is a good correlation between the copies of HBV-DNA and the levels of HBV-LP. HBV-LP expression can reflect the replication of HBV.