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Objectives This study retrospectively investigated in which cycle measurable residual disease (MRD) is associated with prognosis in patients in first complete remission (CR1) of intermediate-risk acute myeloid leukemia (AML). Methods The study enrolled 235 younger patients with intermediate-risk AML. MRD was evaluated by multiparameter flow cytometry after the 1st, 2nd, and 3rd chemotherapy cycles (MRD1–3, respectively). Results No significant association was detected after the 1st and 2nd cycles. However, the 5-year incidence of relapse was higher in the MRD3-positive group (n = 99) than in the negative group (n = 136) (48.7% vs. 13.7%, P = 0.005), while 5-year disease-free survival (DFS) and overall survival (OS) were lower in the MRD3-positive group than in the negative group (43.2% vs. 81.0% and 45.4% vs. 84.1%; P = 0.003 and 0.005, respectively). Allogeneic hematopoietic stem cell transplantation led to a lower 5-year relapse, and higher DFS and OS rates than chemotherapy in the MRD3-positive group (22.3% vs. 71.5%, 65.9% vs. 23.0%, and 67.1% vs. 23.9%; P Conclusions MRD3 could serve as an indicator for post-remission treatment choice and help improve outcomes for intermediate-risk AML in CR1.

Background: Risk stratification for normal karyotype acute myeloid leukemia remains unsatisfactory, which is reflected by the high incidence of leukemia relapse. This study aimed to evaluate the role of gene mutations and clinical characterization in predicting the relapse of patients with normal karyotype acute myeloid leukemia. Methods: A prognostic system for normal karyotype acute myeloid leukemia was constructed based on gene mutations, measurable residual disease, and clinical characteristics. A panel of gene mutations was explored using next-generation sequencing. The least absolute shrinkage and selection operator, and nomogram algorithm were used to build a genomic mutation signature (GMS) nomogram (GMSN) model that combines GMS, measurable residual disease, and clinical factors to predict relapse in 347 patients with normal karyotype acute myeloid leukemia from four centers. Results: Patients in the GMS-high group had a higher 5-year incidence of relapse than those in the GMS-low group (P< 0.001). The 5-year incidence of relapse was also higher in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (P< 0.001). The 5-year disease-free survival and overall survival rates were lower in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (P < 0.001) as confirmed by training and validation cohorts. Conclusions: This study illustrates the potential of GMSN as a predictor of normal karyotype acute myeloid leukemia relapse.

In recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in AML have not been fully elucidated. We found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML. In summary, our research demonstrates that STAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.

BackgroundIn recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in patients with AML have not been fully elucidated.ResultsWe found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high transcription level of STAT6 was associated with low overall survival (OS) in patients with AML. Conversely, high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML.Conclusions STAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P

It has been demonstrated that microRNA-98 (miR-98) is dysregulated in multiple types of solid tumors, but its expression and impact in acute myeloid leukemia (AML) is unclear. To explore the prognostic role of miR-98 in AML, 164 AML patients with the miR-98 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. First, patients were divided into chemotherapy-only (chemotherapy) group and allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was then divided in two groups by the median expression level of miR-98. In chemotherapy group, high miR-98 expression was associated with longer event-free survival (EFS, P = 0.003) and overall survival (OS, P = 0.004), but in allo-HSCT group, EFS and OS were not significantly different between high and low miR-98 expressers. Second, All patients were divided in two groups by the median expression level of miR-98. In low miR-98 expressers, those treated with allo-HSCT had longer EFS (P = 0.001) and OS (P < 0.001) than chemotherapy, but in high miR-98 expressers, survival was independent from treatment modalities. Gene ontology enrichment analysis indicated that the genes associated with miR-98 expression were mainly concentrated in "definitive hemopoiesis", "negative regulation of myeloid cell differentiation" and "signaling pathways regulating pluripotency of stem cells" pathways. In conclusion, our results indicated that high miR-98 expression confers good prognosis in AML patients treated with chemotherapy alone. Patients with low miR-98 expression may benefit from allo-HSCT.

DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. Patients were divided based on treatment modality into the chemotherapy group and the allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was divided into two groups by the median expression levels of DOCK2. In the chemotherapy group, high DOCK2 expression was associated with longer event-free survival (EFS, P=0.001) and overall survival (OS, P=0.007). In the allo-HSCT group, EFS and OS were not significantly different between high and low DOCK2 expression groups. Multivariate analysis showed that high DOCK2 expression was an independent favorable prognostic factor for both EFS and OS in all patients (all P

Taurine-upregulated gene 1 (TUG1) has been reported as an oncogenic long non-coding RNA (lncRNA) in acute myeloid leukemia (AML). Nevertheless, the roles and molecular mechanism of TUG1 in drug resistance of AML cells are still unclear. Glycolysis level was evaluated by detecting glucose consumption and lactate production. qRT-PCR and Western blot were performed to detect TUG1, hexokinase2 (HK2) and pyruvate kinase isoenzyme M2 (PKM2) expressions. Adriamycin (ADR) cytotoxicity and apoptosis were assessed by MTT assay and flow cytometry, respectively. The changes of the protein kinase B (Akt) pathway were determined by Western blot analysis of phosphorylated-Akt (p-Akt) (ser473) and Akt. Our results showed that glycolysis was increased in HL60/ADR cells, as evidenced by the elevated glucose consumption and lactate production, as well as the increased HK2 and PKM2 expressions at mRNA and protein levels. TUG1 was up-regulated in HL60/ADR cells and TUG knockdown inhibited glycolysis. TUG1 knockdown enhanced ADR-induced cytotoxicity and apoptosis in HL60/ADR cells. TUG1 knockdown inhibited the Akt pathway and activation of the Akt pathway by 740Y-P attenuated the effects of TUG1 knockdown on ADR-induced cytotoxicity and apoptosis, as well as glycolysis in HL60/ADR cells. Taken together, TUG1 knockdown enhances adriamycin cytotoxicity in HL60/ADR cells via inhibiting the glycolysis by inactivating the Akt pathway.

Deoxyshikonin was reported to exhibit an anti-tumor effect in colorectal cancer. However, no studies are available to illustrate the effect of deoxyshikonin on acute myeloid leukemia (AML). The effects of deoxyshikonin on viability, apoptosis, caspase-3/7 activity, and cytochrome (Cyt) C expression were evaluated by Cell Counting Kit-8 assay, flow cytometry analysis, caspase-3/7 activity assay, and western blot analysis, respectively. Glucose consumption and lactate production were measured to determine the glycolysis level. The expression of pyruvate kinase M2 (PKM2) was detected by quantitative real-time polymerase chain reaction and western blot analysis. The results showed that deoxyshikonin inhibited cell viability and increased the apoptotic rate, the caspase-3/7 activity, and the Cyt C protein level in AML cells in a dose-dependent manner. Additionally, deoxyshikonin concentration-dependently decreased glucose consumption, lactate production, and PKM2 expression in AML cells. Deoxyshikonin inactivated the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR) pathway. The activation of the Akt/mTOR pathway reversed the effects of deoxyshikonin on viability, apoptosis, and glycolysis in AML cells. In conclusion, deoxyshikonin dampened the viability and the glycolysis of AML cells by suppressing PKM2 via inactivation of the Akt/mTOR signaling.

The purpose of the present study was to investigate whether expression levels of adenylate kinase 1 (AK1) were associated with prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). 85 AML patients with AK1 expression report who received chemotherapy-alone and 71 who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either AK1high or AK1low based on their AK1 expression level relative to the median. Then, overall survival (OS) and event-free survival (EFS) were compared between patients with high vs. low AK1 expression. In the chemotherapy group, high AK1 expression was favorable for both EFS (P=0.016) and OS (P=0.014). In the allo-HSCT group, there was no association for AK1 expression levels and clinical outcomes. Further analyses suggested that in the high AK1 expression group, EFS and OS were longer in patients treated with allo-HSCT compared with those treated with chemotherapy (P=0.0011; P

Increasing evidence showed that long non-coding RNAs (lncRNAs) play critical roles in tumor progression. FEZF1-AS1 is a cancer-associated lncRNA which upregulated and associated with poor prognosis in patients with cancer. However, the roles of FEZF1-AS1 in multiple myeloma (MM) remains unclear. In the present study, our data revealed that FEZF1-AS1 expression was increased both in MM samples and cell lines. Loss of functional assays indicated that FEZF1-AS1 suppression inhibited MM cells proliferation, arrested cell cycle in G0/G1 phase and induced cell apoptosis in vitro. Furthermore, our data indicated that FEZF1-AS1 functioned as a competing endogenous RNA in MM cells that regulated miR-610 expression, which suppressed Akt3. Those data showed that FEZF1-AS1 promoted MM cells proliferation through regulating miR-610/Akt3 axis, suggesting FEZF1-AS1 could be served as a potential target for cancer therapeutics in MM.

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age ≥60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count ≥50×109/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count ≥50×109/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.

The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French–American–British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.

Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, little is known about its functional role and molecular mechanism in MM. The aim of this study was to investigate the clinical and biological significance of CCAT1 in MM. Our data showed that the relative expression levels of CCAT1 were significantly upregulated in MM tissues and cell lines compared with healthy donors and normal plasma cells (nPCs). High expression of CCAT1 was correlated shorter overall survival of MM patients. CCAT1 knockdown significantly inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in vitro, and suppressed tumor growth in vivo. MiR-181a-5p was a direct target of CCAT1, and repression of miR-181a-5p could rescue the inhibition of CCAT1 knockdown on MM progression. In addition, CCAT1 positively regulated HOXA1 expression through sponging miR-181a-5p in MM cells.taken together, lncRNA CCAT1 exerted an oncogenic role in MM by acting as a ceRNA of miR-181a-5p. These results suggest that CCAT1 may serve as a novel diagnostic marker and therapeutic target for MM.

HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that is highly specific for maturing myeloid cells. Dysregulation of HOTAIRM1 has been found to be implicated in the development of acute myeloid leukemia (AML). However, the role of HOTAIRM1 in the drug resistance in AML remains unknown. The present study aimed to investigate the effect of HOTAIRM1 on the cytarabine (Ara-C) resistance in leukemia cell lines and to explore the underlying mechanism. The leukemia cell lines, HL60 and THP-1, were transfected with HOTAIRM1 specific siRNA (si-HOTAIRM1) or control siRNA (si-ctrl), and then treated with Ara-C for 48 h. The mRNA levels of HOTAIRM1 and platelet-type phosphofructokinase (PFKP) were measured using RT-PCR. Cell viability was evaluated by MTT assay. Apoptosis was determined using flow cytometry and caspase-3/7 activity assay. Glycolysis was evaluated by determining the glucose consumption and lactate production. To activate the Wnt/β-catenin signaling pathway, HL60 and THP-1 cells were transfected with β-catenin overexpressing plasmid (pcDNA-β-catenin). Protein levels of PFKP, β-catenin, and c-Myc were examined using western blot analysis. The results showed that knockdown of HOTAIRM1 enhanced Ara-C-induced reduction of cell viability and increase of cell apoptosis. HOTAIRM1 knockdown suppressed the glucose consumption and lactate production, as well as the expression of PFKP in AML cells. Besides, HOTAIRM1 knockdown resulted in a significant inhibitory effect on the Wnt/β-catenin pathway. Furthermore, activating Wnt/β-catenin pathway mitigated the effects of HOTAIRM1 knockdown on glycolysis and Ara-C cytotoxicity in AML cells. In conclusion, knockdown of HOTAIRM1 enhanced Ara-C cytotoxicity through regulating the Wnt/β-catenin/PFKP signaling pathway. These findings suggested that HOTAIRM1 might be a therapeutic target for overcoming the Ara-C resistance in AML.

LncRNAs have been shown to be involved in the biological and pathological processes of acute myeloid leukemia (AML). Hox antisense intergenic RNA myeloid 1 (HOTAIRM1) was reported to be highly expressed in AML. However, the detailed role and molecular mechanism of HOTAIRM1 in AML pathogenesis remain undefined. In the present study, HOTAIRM1 and miR-148b expressions in AML patients and healthy controls were detected by qRT-PCR. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry assays, respectively. The regulatory interaction between HOTAIRM1 and miR-148b was explored by bioinformatics analysis using starBase v3.0 software and The Cancer Genome Atlas (TCGA) AML dataset. We found that the miR-148/miR-152 family members including miR-148a, miR-148b, and miR-152 were predicted to be potential targets of HOTAIRM1. HOTAIRM1 expression was negatively correlated with miR-148b expression but had no correlation with miR-148a/miR-152 expressions in AML samples from the TCGA dataset. HOTAIRM1 expression was higher while miR-148b expression was lower in AML patients than in healthy controls. A negative correlation between HOTAIRM1 and miR-148b in AML patients was observed. HOTAIRM1 silencing and miR-148b overexpression both suppressed cell proliferation and induced apoptosis in AML cells. miR-148b was identified as a target of HOTAIRM1 in AML cells. Moreover, HOTAIRM1 knockdown inhibited proliferation and induced apoptosis in AML cells by negatively regulating miR-148b. In summary, HOTAIRM1 was involved in the progression of AML through targeting miR-148b, shedding light on the biological function and molecular mechanism of HOTAIRM1 in AML.

Adriamycin (ADR) is a widely used drug in multiple cancers including leukemia. Artesunate (ART) has been reported to improve the cytotoxicity of some chemotherapeutic drugs in cancers. However, it is still unknown whether ART can augment the cytotoxicity of ADR in ADR-resistant K562 leukemia cells (K562/ADR). Glycolytic activity was assessed by detecting glucose consumption, lactate production and glycolysis-related enzymes. MDR1 and ABCG2 mRNA levels were measured by RT-qPCR. Protein levels of P-glycoprotein (P-gp), ABCG2 and cytochrome c (Cyt c) were determined by western blot assay. Cell apoptosis was evaluated by flow cytometry. Cell viability was examined by CCK-8 assay. The results showed that K562/ADR cells exhibited increased glycolytic activity and mdr1 and abcg2 gene expression. ART potentiated ADR cytotoxicity in K562 and K562/ADR cells. Moreover, ART reversed ADR-induced mdr1 and abcg2 gene expression and inhibited P-gp and ABCG2 activities in K562/ADR cells. ART potentiated ADR-mediated inhibition on glycolysis in K562 and K562/ADR cells. Inhibition of glycolysis reduced cell viability, downregulated the expression of mdr1 and abcg2 genes, and induced cell apoptosis in K562/ADR cells. Overall, the results indicated that ART enhanced ADR cytotoxicity by inhibiting glycolysis and reducing mdr1 and abcg2 gene expression in K562/ADR cells, providing a deep insight into the function and molecular basis of ART in regulating MDR in leukemia cells and hinting at the potential values of ART in alleviating MDR in cancers.

Overexpression of microRNA-99a (miR-99a) have been associated with adverse prognosis in acute myeloid leukemia (AML). Nevertheless, whether it also predicts poor outcome in post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) AML patients remains unclear. To further elucidate the prognostic value of miR-99a, 74 AML patients with miR-99a expression report who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either miR-99ahigh or miR-99alow based on their miR-99a expression levels relative to the median. Two groups had similar clinical and molecular characteristics except that miR-99ahigh group had fewer patients of the French-American-British M4 subtype (P = 0.018) and more frequent CEBPA mutations (P = 0.005). Univariate analysis indicated that high miR-99a expression was unfavorable for both event-free survival (EFS) and overall survival (OS; P = 0.029; P = 0.012, respectively). Multivariate analysis suggested that high miR-99a expression was an independent risk factor for both EFS and OS in AML patients who underwent allo-HSCT [hazard ratio (HR) 1.909, 95% confidence interval (CI) 1.043–3.494, P = 0.036 and HR 2.179, 95% CI 1.192–3.982, P = 0.011, respectively]. Our results further proved that high miR-99a expression could predict worse outcome in AML patients, even in those who underwent intensive post-remission therapy such as allo-HCST.

The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French-American-British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cure for intermediate or adverse-risk acute myeloid leukemia (AML) (1). It offers patients longer overall survival (OS) (2-4). Unfortunately, human leukocyte antigen (HLA) matched related donor is unavailable in more than 70% patients. Some of these patients, may experience relapse and subsequently achieve CR (non-CR1) with treatment. Some non-CR1 patients eventually receive allo-HSCT. It is unclear whether allo-HSCT will improve the survival of these patients.

Drug resistance remains a major cause of relapse and therapeutic failure in acute myeloid leukemia (AML). Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been documented to act as an oncogene and is frequently highly expressed in human cancers including AML. However, the function and molecular mechanism of MALAT1 in regulating cytarabine (Ara-C) resistance of AML are largely unknown. The expressions of MALAT1 and miR-96 in AML patients and healthy controls were examined by qRT-PCR. CCK-8 and flow cytometry assay were performed to assess the proliferation and apoptosis of AML cells. The interaction between MALAT1 and miR-96 was investigated by luciferase reporter assay. We found that MALAT1 was upregulated while miR-96 was downregulated in AML patients compared with healthy controls. A negative correlation between MALAT1 and miR-96 expressions was observed in AML patients. Knockdown of MALAT1 inhibited the proliferation, induced apoptosis, and enhanced Ara-C sensitivity of AML cells. Additionally, MALAT1 suppressed miR-96 expression by acting as a molecular sponge of miR-96 in AML cells. miR-96 downregulation abolished the effects of MALAT1 knockdown on the proliferation, apoptosis, Ara-C sensitivity in AML cells. In conclusion, MALAT1 knockdown inhibited proliferation, promoted apoptosis and enhanced Ara-C sensitivity in AML cells by upregulating miR-96, providing novel insights into the critical role of MALAT1 as a miRNA sponge in AML.