Efficacy and safety of decitabine combined with low-dose cytarabine, aclarubicin, and granulocyte colony-stimulating factor compared with standard therapy in acute myeloid leukemia patients with TP53 mutation

Tumor suppressor gene P53(TP53)is a critical tumor suppressor gene.The mutant p53 protein enhances the activity,invasion and metastasis of tumor cells.Acute myeloid leukemia(AML)patients with TP53 mutations respond poorly to conventional chemotherapy and have poor clinical outcomes.We previously conducted a multi-center phase II clinical trial(No.ChiCTRONC-11001700)in elderly AML patients with decitabine,low-dose cytarabine,aclarubicin,and granulocyte colony-stimulating factor(G-CSF)(DCAG regimen),which showed an overall response rate(ORR)of 82.4%and a complete remission(CR)rate of 64.7%.[1]Given this satisfactory effect of DCAG regimen,the present study has been designed to compare the efficacy and safety of DCAG regimen with standard therapy in AML patients with TP53 mutations.

Overexpression of c-Myc-dependent heterogeneous nuclear ribonucleoprotein A1 promotes proliferation and inhibits apoptosis in NOTCH1-mutated chronic lymphocytic leukemia cells

Background: NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients withNOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused byNOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1).Methods: The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.Results: RNA splicing was found to play a vital part inNOTCH1-mutated CLL cells;hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primaryNOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition.Conclusion: Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis inNOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients withNOTCH1 mutation.

Bortezomib depended on PRDM1 and TP53 to exert therapeutic effect in activated B-cell-like diffuse large B-cell lymphoma

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BLIMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior survival.However,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of PRDM1.We investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal inactivation.We first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

Chidamide-BEAC plus autologous stem cell transplantation in high-risk non-Hodgkin lymphoma:a phase II clinical trial

To the Editor:Non-Hodgkin lymphoma(NHL)is a common type of hematological malignancy.Although the development of targeted therapies has improved the survival of patients with aggressive NHL,autologous hematopoietic stem cell transplantation(HSCT)remains indispensable.There is no standard conditioning regimen for autologous stem cell transplantation(ASCT).

EBV-Mir-BART5-5p targets p53 independent pathway in cytoplasm:Potential role in EBV lymphomagenesis

EBV-positive diffuse large B-cell lymphoma(DLBCL),which has a clonal EBV carrying proliferation of B-cells,defines a new DLBCL subtype and predicts a poor prognosis.Further studies are needed to explore the underlying mechanisms in EBV lymphomagenesis.EBV encoded microRNAs(miRNAs)have been proven to contribute to the pathogenesis and oncogenesis of EBV-associated malignancies.^(1)In this study,research has focused on the pathological roles of miRNAs in EBV-positive DLBCL progression and survival,which might provide ideas for therapeutic decision to improve the prognosis.

Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical outcomes.Patients who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely dismal prognosis.The heterogeneous clinical outcomes of DLBCL patients result from variable genetic profiles.