A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

[Apoptosis of in vitro cultured BMMNC from MDS patients induced by arsenic sulfide].

The aim of this study was to investigate the inhibition effect of arsenic sulfide (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTT, flow cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0-0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2) after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows no inhibition effect on proliferation of MDS cells; high concentration of As2S2 (1.5-50 mg/L) induces apoptosis of MDS cells.