RNA-binding protein NOVA1 promotes acute T-lymphocyte leukemia progression by stabilizing USP44 mRNA.

Acute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with NOVA1, and RNA immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. The knockdown of NOVA1 had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function might be achieved by binding to and stabilizing USP44 mRNA.

Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report.

Currently, arsenic trioxide therapy is widely used for the treatment of acute promyelocytic leukemia (APL), relapsed and refractory adult T-cell leukemia/lymphoma and myelodysplastic syndrome. Regarding the broad antitumor activity of arsenic, certain studies have been undertaken to test its efficacy in treating acute T-cell lymphoblastic leukemia (T-ALL) cell lines and patients; however, to the best of our knowledge, no reports document that arsenic is able to induce the remission of T-ALL patients. The present study reports the case of young male patient diagnosed with T-ALL, with no significant response to common chemotherapy regimens, who finally achieved complete remission without minimal residual disease (as detected by flow cytometry) due to arsenic treatment. This result is encouraging, and the present study has shown that malignant TCRαß+ cell clones can be detected at the molecular level using reverse transcription-polymerase chain reaction (PCR) combined with the GeneScan technique. The result is mainly based on the T-cell receptor (TCR) Vß1 clone (a 190-base pair PCR product that with the same complementarity determining region 3 length can be detected for all samples collected during various statuses) and on undetectable TCR Vγ subfamily members, at the time of disease diagnosis. It is important to analyze the dynamically changing TCR pool in leukemia patients during therapy. Although the molecular mechanism through which arsenic contributes to malignant clone elimination remains unclear in the case presented, the use of arsenic is expected to be effective for clinically treating refractory and relapsed T-ALL patients.