Side population (SP) cells are involved in the development of multidrug resistance (MDR) in human multiple myeloma (MM), due to their cancer stem cell (CSC)‑like phenotypes. ATP‑binding cassette (ABC) drug transporter proteins have been reported to be closely associated with MDR in leukemia; however, the correlation between ABC proteins and the progression of MM remains unclear. The present study used MM cell lines and clinical samples to determine the role of ABC subfamily G member 2 (ABCG2) in MM via flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blotting. SP cells sorted from MM cell lines, including NCI‑H929 cells, via fluorescence‑activated cell sorting, exhibited CSC‑like phenotypes and expressed high levels of ABCG2. Expression of ABCG2 and activation of the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was positively associated with the proportion of SP cells in the NCI‑H929 cell line. In addition, suppression of the PI3K/AKT pathway using LY294002 or rapamycin counteracted the protective effects of ABCG2 against chemotherapeutic drug treatment. Mechanistically, PI3K/AKT signaling may regulate ABCG2 expression, and ABCG2 may regulate phosphatase and tensin homolog expression via a potential negative feedback loop. Furthermore, SP cell proportion, ABCG2 expression and PI3K/AKT pathway activation were associated with disease progression in patients with MM. These findings indicated the critical roles of ABCG2 and PI3K/AKT signaling in controlling stemness of MM cells, and suggested a novel strategy for targeting ABCG2 and PI3K/AKT signaling to treat MM with MDR.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV), which is classified into the genus Phlebovirus and family Phenuiviridae. Reactive plasmacytosis mimicking multiple myeloma is a very rare condition in association with SFTS. Here, we describe two SFTS cases who presented with hyperimmunoglobulinemia, as well as extensive bone marrow and peripheral blood plasmacytosis, which mimicked multiple myeloma (MM). We report two cases who presented with fever and blood routine abnormity which were conformed as SFTS eventually. They were performed bone marrow aspiration and were admitted to the department of hematology with a preliminary diagnosis of MM. They all had hyperimmunoglobulinemia, extensive bone marrow and peripheral blood plasma cells, prolonged activated partial thromboplastin time (APTT), elevated hepatic enzyme. The two patients recovered with treatment of doxycycline, human immunoglobulins, plasma transfusion, and other supporting treatments. But case 1 occurred lymphoma 8 months later and died. SFTS might be one of differential diagnosis of MM in certain endemic area. We also conclude that SFTSV is a pantropic virus that could injure most tissues and cells of the human body.

To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs) of acute myeloid leukemia-M5 (AML-M5), R-banding karyotype, oligonucelotide array CGH and FISH were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than 5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations were mapped. Seven out of them were described in the previous AML studies and five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2-qter was the sole large recurrent chromosomal anomaly and the pathogenic mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26 abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a common marker of myeloid leukemia rather than a specific marker for AML-M5 subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were noted and it might be associated with AML-M5. The number of CNA did not show a significant association with clinico-biological parameters and CR number of the 22 patients received chemotherapy. This study provided the evidence that array CGH served as a complementary platform for routine cytogenetic analysis to identify those cryptic alterations in the patients with AML-M5. As a subtype of AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor novel oncogenes or tumor suppressor genes. Clarifying the role of these genes will contribute to the understanding of leukemogenic network of AML-M5.

MicroRNA (miR)-148a is differentially expressed in numerous malignant tumors and it was identified to regulate tumor growth, cell proliferation, apoptosis, angiogenesis and drug resistance via the regulation of the expression levels of its target genes. However, the biological function of miR-148a in acute myeloid leukemia (AML) and its molecular mechanisms of action remain unclear. In the present study, the expression levels of miR-148a and DNA methyltransferase 1 (DNMT1) were detected using reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting. Methylation-specific PCR was used to detect the methylation levels in the miR-148a promoter. The effects of miR-148a on cell proliferation and apoptosis were assessed by Cell Counting kit-8 or flow cytometry assays, respectively. A dual-luciferase reporter assay was performed to investigate the association between miR-148a and DNMT1. Patients with AML exhibited an increased expression level of miR-148a, whereas the expression level of DNMT1 was identified to be decreased compared with healthy control subjects. In AML cell lines, the methylation state of miR-148 promoter was significantly increased compared with normal cells. Following knockdown of DNMT1 in U937 cells, the expression level of miR-148a increased significantly, whereas the methylation level of the miR-148a promoter decreased. The mRNA and protein expression levels of DNMT1 decreased following transfection with miR-148a mimics in U937 cells. Conversely, transfection with miR-148a inhibitor in Kasumi-1 cells led to an increase in the expression level of DNMT. Dual-luciferase reporter assays suggested that DNMT1 was one of the direct target genes of miR-148a. Overexpression of miR-148a inhibited cell proliferation and promoted apoptosis. Inhibition of DNMT1 led to a decreased methylation level of the 5-cytosine-phosphate-guanine-3 islands in the miR-148a promoter, thus increasing the expression level of miR-148a. DNMT1 was identified to be a downstream target of miR-148a, and was negatively regulated by miR-148a in AML cell lines, suggesting that miR-148a and DNMT1 form a mutual negative feedback loop.

DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia.