Comparison of long-term outcomes between imatinib and dasatinib prophylaxis after allogeneic stem cell transplantation in patients with Philadelphia-positive acute lymphoblastic leukemia: A multicenter retrospective study.

BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. RESULTS: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. CONCLUSIONS: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib.

Detection methods and prognosis implications of measurable residual disease in acute myeloid leukemia.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) refers to the quantity of residual leukemic cells in a patient after treatment.According to the latest agreements, MRD in AML offering essential prognostic insights. However, there is ongoing debate regarding MRD-based monitoring and treatment strategies. There are multiple platforms for detecting MRD, each varying in sensitivity and suitability for different patients. MRD not only predicts treatment outcomes but also serves as an indicator of treatment effectiveness and a prognostic biomarker. In AML, most retrospective studies indicate that patients who are MRD-positive or show increasing MRD levels at specific time points during remission have significantly higher risks of relapse and mortality compared to MRD-negative patients. Although achieving MRD-negative status can improve patient prognosis, the possibility of relapse remains. Despite the correlation between MRD and clinical outcomes, MRD assessment methods are not yet standardized, leading to discrepancies in results across different techniques. To provide reliable MRD results, it is essential to optimize and standardize MRD detection methods. Methods for assessing MRD include multiparameter flow cytometry (MFC) and molecular assays, chosen based on disease characteristics. This review focuses on currently available MRD detection methods and discusses how the prognostic value of MRD test results informs personalized treatment strategies for AML patients.

Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study.

Chronic myelomonocytic leukemia (CMML) is a rare and aggressive myeloid malignancy with overlapped features of myelodysplastic syndromes/myeloproliferative neoplasms. Azacitidine (AZA), a hypomethylating agent, has been approved for the treatment of CMML in China, but real-world data are limited. Medical records of CMML patients who had received subcutaneously injected AZA were reviewed from January 2018 at five participating sites in China. Response was assessed according to the modified International Working Group (IWG 2006) criteria. Between January 2018 and November 2020, a total of 24 patients with CMML were included with a median age of 63 years. Patients received a median of 3 cycles of AZA treatment (range, 1-8). Overall response rate (ORR) was 37.5% (9 of 24); CR rate, PR rate, and mCR/HI rate were 8.3% (n = 2), 8.3% (n = 2), and 20.8% (n = 5), respectively. At a median duration of follow-up of 14.0 months (range 0.0-22.0 months), the median overall survival (OS) was 23.0 months. Univariate analysis revealed that ≥ 3 cycles of treatment was significantly associated with a higher 1-year OS rate compared with < 3 cycles of AZA treatment. Treatment was generally well-tolerated. The most common (> 10%) AEs were thrombocytopenia (n = 7, 29.2%), pneumonitis (n = 4, 16.7%) and fever (n = 3, 12.5%). This study provides valuable real-life data in China on the treatment schedules, efficacy and safety of AZA in the treatment of CMML.

Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area.

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs-negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs-positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation.

Outcome after allogeneic hematopoietic stem cell transplantation following Venetoclax-based therapy among AML and MDS patients.

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.

Safety and efficacy of a humanized CD19 chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic leukemia.

CD19-targeted chimeric antigen receptor T (CAR-T) cells using murine single-chain variable fragment (scFv) has shown substantial clinical efficacy in treating relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, potential immunogenicity of the murine scFv domain may limit the persistence of CAR-T cells. In this study, we treated 52 consecutive subjects with R/R ALL with humanized CD19-specific CAR-T cells (hCART19s). Forty-six subjects achieved complete remission (CR) (N = 43) or CR with incomplete count recovery (CRi) (N = 3) within 1 month post infusion. During the follow-up with a median time of 20 months, the 1-year cumulative incidence of relapse was 25% (95% confidence interval [CI] 13-46), and 1-year event-free survival was 45% (95% CI 29-60). To the cutoff date, 20 patients presented CD19+ relapse and 2 had CD19- relapse. Among the 22 relapsed patients, 14 had treatment-mediated and treatment-boosted antidrug antibodies (ADA) as detected in a sensitive and specific cell-based assay. ADA positivity was correlated with the disease relapse risk. ADA-positive patients had a significantly lower CAR copy number than ADA-negative patients at the time of recurrence (p < .001). In conclusion, hCART19s therapy is safe and highly active in R/R ALL patients, and the hCART19s treatment could induce the emergence of ADA, which is related to the recurrence of the primary disease.

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial.

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m2 daily, days 1 to 3; idarubicin, 6 mg/m2 daily, days 4 to 6; cytarabine 25 mg/m2 every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 µg/kg, from day 4 until neutrophil count increased to 1.0 × 109 /L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.

Ruxolitinib combined with etanercept induce a rapid response to corticosteroid-refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi-center prospective study.

About half of patients with severe acute graft vs host disease (aGVHD) show resistance to treatment with first-line steroids. We enrolled 64 patients with grades III-IV SR-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT), to assess the efficacy and safety of the combination therapy of ruxolitinib and etanercept. The overall response rate was 87.5% (95% CI, 79.7%-95.3%) at day 28 of the combination treatment, from which 73.4% reached complete response (CR). A marked reduction ≥75% in daily corticosteroid dosing was documented in 75.4% of patients at day 28. Delayed time from aGVHD to ruxolitinib (OR = 4.88, 95% CI, 0.98-23.56), stages 3-4 liver aGVHD (OR = 8.57, 95% CI, 0.96-46.59) and gut Enterobacteriaceae colonization (OR = 12.39, 95% CI, 1.71-59.77) were related to incomplete response. Grades 3/4 anemia, leukopenia, or thrombocytopenia and CMV-reactivation were found in 29.7%, 26.6%, 39.1%, and 50.0% of patients, respectively. So, 25 (39.1%) experienced complications of severe infection ≥3 grade, in which pulmonary infections were most frequent (15/64, 23.4%). The 2-year overall survival (OS) after the combination therapy was 61.2%. The 2-year incidence of non-relapse mortality and relapse of the underlying malignancy was 26.7% and 15.7%, respectively. Combined treatment with ruxolitinib and etanercept was very effective and relatively safe for severe aGVHD patients, while the various infection complications deserve more attention. This study was registered at the Chinese Clinical Trial Registry (ChiCTR1900024408).

Long non-coding RNA SNHG16 has Tumor suppressing effect in acute lymphoblastic leukemia by inverse interaction on hsa-miR-124-3p.

Acute lymphoblastic leukemia (ALL) is one of the deadly forms of childhood cancers in the world. In the present study, we used both in vitro and in vivo models to evaluate the functional mechanisms of a long noncoding RNA (lncRNA), small nucleolar RNA host gene 16 (SNHG16) in ALL. SNHG16 gene expression was evaluated by quantitative real-time PCR (qPCR) in both in vitro ALL cell lines and in vivo human samples of T lymphocytes. Lentivirus-mediated SNHG16 downregulation was performed in MOLT3 and SUP-B15 cells, to evaluate its functional effects on ALL cell proliferation, migration in vitro, and ALL transplant in vivo. Epigenetic regulation of SNHG16 on human miR-124-3p (hsa-miR-124-3p) was evaluated by dual-luciferase activity assay and qPCR. Hsa-miR-124-3p was inhibited in SNHG16-downregulated MOLT3 and SUP-B15 cells to further evaluate the functional correlation between SNHG16 and hsa-miR-124-3p in ALL. SNHG16 is upregulated in both in vitro ALL cell lines and in vivo human leukemic T-cells. SNHG16 downregulation suppressed ALL proliferation and migration in vitro, and ALL explant in vivo. Hsa-miR-124-3p was demonstrated to interact with SNHG16, and upregulated in SNHG16-downregulated ALL cells. In addition, inhibiting hsa-miR-124-3p reversed SNHG16-downregulation-mediated tumor suppressive functions in ALL. SNHG16 is upregulated in ALL, and its inhibition has tumor suppressive effect in ALL, likely through epigenetic interaction on hsa-miR-124-3p. © 2018 IUBMB Life, 71(1):134-142, 2019.

Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001-2013.

BACKGROUND/AIM: As the knowledgebase of acute myeloid leukemia (AML) has grown, classification systems have moved to incorporate these new findings. METHODS: We assessed 32,941 patients with AML whose records are contained in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Half of all patients diagnosed between 2001 and 2013 did not have a World Health Organization (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with myelofibrosis were associated with the longest leukemia-specific survival (110 and 115 months, respectively), and AML with minimal differentiation and acute megakaryoblastic leukemia with the shortest (30 and 28 months, respectively). For patients in the WHO groups AML not otherwise specified (AML-NOS) and AML with recurrent genetic abnormalities (AML-RGA), the risk of death was greater for older patients and less for married patients. Black patients with any type of AML-NOS also had a higher risk of death. Patients whose case of AML did not receive a WHO classification were older and this group had a higher risk of death when compared to patients with a WHO type of AML-NOS. CONCLUSION: Our findings highlight the divergent outcomes of patients with AML and the importance of using the WHO classification system and demographic factors to gauge their prognosis.

The 68-kDa telomeric repeat binding factor 1 (TRF1)-associated protein (TAP68) interacts with and recruits TRF1 to the spindle pole during mitosis.

The telomere capping protein TRF1 is a component of the multiprotein complex "shelterin," which organizes the telomere into a high order structure. Besides telomere maintenance, telomere-associated proteins also have nontelomeric functions. For example, tankyrase 1 and TRF1 are required for the maintenance of faithful mitotic progression. However, the functional relevance of their centrosomal localization has not been established. Here, we report the identification of a TRF1-binding protein, TAP68, that interacts with TRF1 in mitotic cells. TAP68 contains two coiled-coil domains and a structural maintenance of chromosome motifs and co-localizes with TRF1 to telomeres during interphase. Immediately after nuclear envelope breakdown, TAP68 translocates toward the spindle poles followed by TRF1. Dissociation of TAP68 from the telomere is concurrent with the Nek2A-dependent phosphorylation at Thr-221. Biochemical characterization demonstrated that the first coiled-coil domain of TAP68 binds and recruits TRF1 to the centrosome. Inhibition of TAP68 expression by siRNA blocked the localization of TRF1 and tankyrase 1 to the centrosome. Furthermore, siRNA-mediated depletion of TAP68 perturbed faithful chromosome segregation and genomic stability. These findings suggest that TAP68 functions in mediating TRF1-tankyrase 1 localization to the centrosome and in mitotic regulation.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis.

BACKGROUND: MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathways of MiR-125b in gastric cancer. METHODS: We investigated MiR-125b expression in fresh tissues from 50 gastric cancer patients and 6 gastric cancer cell lines using RT-PCR, and explored its prognostic value by hybridizing MiR-125b in situ for 300 clinical gastric tumor tissues with pathological diagnosis and clinical parameters. The effects of MiR-125b on gastric cancer cells and downstream target genes and proteins were analyzed by MTT, transwell assay, RT-PCR, and western blot on the basis of silencing MiR-125b in vitro. Luciferase reporter plasmid was constructed to demonstrate MiR-125b's direct target. RESULTS: MiR-125b was upregulated in gastric cancer tissues and cell lines, and significantly promoted cellular proliferation, migration, and invasion by downregulating the expression of PPP1CA and upregulating Rb phosphorylation. MiR-125b expression was significantly correlated with tumor size and depth of invasion, lymph nodes, distant metastasis, and TNM stage. The high-MiR-125b-expression group had a significantly poorer prognosis than the low-expression group (P < 0.05) in stages I, II, and III, and the 5-year survival rate in of the high-expression group was significantly lower than that of the low-expression group. CONCLUSIONS: MiR-125b functions as an oncogene by targeting downregulated PPP1CA and upregulated Rb phosphorylation in gastric cancer. MiR-125b not only promotes cellular proliferation, migration, and invasion in vitro, but also acts as an independent prognostic factor in gastric cancer.

TNFAIP3 Overexpression Inhibits Diffuse Large B-Cell Lymphoma Progression by Promoting Autophagy through TLR4/MyD88/NF-κB Signaling Pathway.

BACKGROUND: Tumor necrosis factor alpha induced protein 3 (TNFAIP3) is reportedly to have significant implications for autophagy regulation in various cancers. The current study aimed to decipher the role and mechanism of TNFAIP3 in diffuse large B-cell lymphoma (DLBCL) by modulating autophagy. METHODS: Information pertaining to the differential expression and prognostic role of TNFAIP3 in DLBCL was gleaned from the Gene Expression Omnibus (GEO) database. The TNFAIP3 expression levels in human DLBCL cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and colony formation assays were employed to determine cell proliferation. Transwell assay and flow cytometry were applied to detect cell migration and apoptosis, respectively. Immunofluorescence and transmission electron microscope were used for the assessment of cell autophagy. The levels of apoptotic markers (caspase-3, cleaved-caspase-3, Bcl-2 Associated X (Bax), and B cell lymphoma-2 (Bcl-2)), autophagy indicators (the ratio of microtubule-associated proteins 1A/1B light chain 3 II and I (LC3II/LC3I), Sequestosome (p62)), and pathway proteins (toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), Transcription Factor NF-Kappa-B P65 Subunit (p65), and phosphorylated-p65 (p-p65)) were assessed via Western blotting. Immunohistochemistry was employed to detect Ki67 expression in tumor tissues. RESULTS: TNFAIP3 expression in DLBCL samples was downregulated, correlating with poor prognosis. TNFAIP3 expression was also downregulated in DLBCL cells. It was found that TNFAIP3 impeded cell proliferation and migration, and enhanced apoptosis of OCI-LY3 cells. Intervention with autophagy inhibitor 3-methyladenine (3-MA) markedly reversed apoptosis of OCI-LY3 cells induced by TNFAIP3. Besides, TNFAIP3 induced autophagy via modulating the TLR4/MyD88/nuclear factor kappa B (NF-κB) signaling pathway. In vivo experiments showed that TNFAIP3 expression in DLBCL was downregulated, and upregulation of TNFAIP3 could inhibit tumor growth. CONCLUSION: TNFAIP3 inhibits DLBCL progression by inducing TLR4/MyD88/NF-κB pathway-mediated autophagy.

Phosphorylation of Tara by Plk1 is essential for faithful chromosome segregation in mitosis.

Trio-associated repeat on actin (Tara) is an F-actin binding protein and regulates actin cytoskeletal organization. In our previous study, we have found that Tara associates with telomeric repeat binding factor 1 (TRF1) and mediates the function of TRF1 in mitotic regulation. We also found that overexpression HECTD3, a member of HECT E3 ubiquitin ligases, enhances the ubiquitination of Tara in vivo and promotes the degradation of Tara, and such degradation of Tara facilitates cell cycle progression. However, less is known about the post-translational modification of Tara in mitosis. Here we show that Tara is a novel Polo-like kinase 1 (Plk1) target protein. Plk1 interacts with and phosphorylates Tara in vivo and in vitro. Actually, the Thr-457 in Tara was a bona fide in vivo phosphorylation site for Plk1. Interestingly, we found that the centrosomal localization of Tara depended on the Thr-457 phosphorylation and the kinase activity of Plk1. Furthermore, overexpression of non-phosphorylatable mutant of Tara caused aberrant mitosis delay in HeLa cells. Our study demonstrated that Plk1-mediated phospho-dependent centrosomal localization of Tara is important for faithful chromosome segregation, and provided novel insights into understanding on the role of Plk1 in cooperation with Tara in mitotic progression.

Dysbiosis and primary B-cell immunodeficiencies: current knowledge and future perspective.

According to Elie Metchnikoff, an originator of modern immunology, several pivotal functions for disease and health are provided by indigenous microbiota. Nonetheless, important mechanistic insights have been elucidated more recently, owing to the growing availability of DNA sequencing technology. There are 10 to 100 trillion symbiotic microbes (such as viruses, bacteria, and yeast) in each human gut microbiota. Both locally and systemically, the gut microbiota has been demonstrated to impact immune homeostasis. Primary B-cell immunodeficiencies (PBIDs) are a group of primary immunodeficiency diseases (PIDs) referring to the dysregulated antibody production due to either intrinsic genetic defects or failures in functions of B cells. Recent studies have found that PBIDs cause disruptions in the gut's typical homeostatic systems, resulting in inadequate immune surveillance in the gastrointestinal (GI) tract, which is linked to increased dysbiosis, which is characterized by a disruption in the microbial homeostasis. This study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the crosstalk between the gut microbiome and PBID, the factors shaping the gut microbiota in PBID, as well as the potential clinical approaches for restoring a normal microbial community.

Therapeutic applications of toll-like receptors (TLRs) agonists in AML.

Acute myeloid leukemia (AML) is an aggressive type of blood cancer affecting bone marrow (BM). In AML, hematopoietic precursors are arrested in the early stages of development and are defined as the presence of ≥ 20% blasts (leukemia cells) in the BM. Toll-like receptors (TLR) are major groups of pattern recognition receptors expressed by almost all innate immune cells that enable them to detect a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns to prime immune responses toward adaptive immunity. Because TLRs are commonly expressed on transformed immune system cells (ranging from blasts to memory cells), they can be a potential option for developing efficient clinical alternatives in hematologic tumors. This is because several in vitro and in vivo investigations have demonstrated that TLR signaling increased the immunogenicity of AML cells, making them more vulnerable to T cell-mediated invasion. This study aimed to review the current knowledge in this field and provide some insight into the therapeutic potentials of TLRs in AML.