Background: The immunomodulatory enzyme, indoleamine 2,3-dioxygenase (IDO) facilitates tryptophan catabolism at the rate-limiting step of the kynurenine (Kyn) pathway. IDO expression and elevations in Kyn metabolites are associated with immunosuppressive tumor microenvironment including T cell proliferative arrest and generation of regulatory T cells (Tregs) which can favor tumor progression. However, the extent of the role of IDO in acute myeloid leukemia (AML) is currently ill-defined. This study reviews the role of IDO-driven Treg function in AML and evaluates the current body of evidence implicating IDO in AML pathogenesis. Method: Studies related to IDO in AML were identified through a systematic review of PubMed and Scopus. Data extracted described sample analysis, IDO expression, IDO in prognosis, techniques used in Treg phenotypic studies, and the effect of IDO inhibitors. Results: Twenty studies were included in the systematic review. Expression of IDO was identified in a range of cells in AML, both inducible and constitutive. Seven studies indicated an association between elevated expression and poor clinical prognosis. Six studies suggested a positive correlation between IDO expression and Treg induction, with FoxP3 being the prominent Treg phenotypic marker. Of eight studies investigating IDO inhibition, some reported reductions in Treg frequency and enhanced effector T cell proliferation. Conclusion: This review highlights that IDO expression in AML is associated with poor prognosis and measurement of IDO and its Kyn metabolites may offer utility as prospective prognostic markers. Pharmacological inhibition of IDO using novel drugs may hold promise for the treatment of AML.

Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. Aim: To clarify the role of miRNAs as biomarkers through a systematic review. Results: From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. Conclusion: These signatures could refine classification and risk stratification of patients and improve ALL outcome.

Background: Approximately, one-third of adult patients with acute myeloid leukemia (AML) are refractory to initial induction chemotherapy and relapse occurs in most patients who achieve remission. This study evaluates the efficacy of decitabine in the management of refractory or relapsed AML. Methods: After literature search in electronic databases (Google Scholar, Embase, Ovid, and PubMed) studies were selected by following pre-determined eligibility criteria. Random-effects meta-analyses were performed to achieve effect sizes of complete remission (CR) rate, response rate (RR), and median survival after therapy. Subgroup analyses were performed with regards to use of decitabine with either epigenetics-based therapy, molecular therapy or chemotherapy. Results: Twenty studies were included (310 patients; age 55.1 years [95% confidence interval (CI): 43.8, 66.4]; 57% [52%, 63%] males). Overall RR was 46.1% [95% CI: 36.1%, 56.1%]. Overall CR rate was 23.5% [95% CI: 22.1%, 24.9%] but was 14.85% [95% CI: 3.8%, 25.9%] for decitabine with epigenetics-based therapies, 15.4% [95% CI: 6.7%, 24.0%] for decitabine with immunotherapy or molecular therapy, 34.8% [95% CI: 18.7%, 50.9%] for decitabine with chemotherapy, and 37.5% [36.4%, 38.7%] for decitabine with chemotherapy and molecular therapy. Median survival was 7.2 months [95% CI: 5.17, 9.3]. Major adverse events were neutropenia, nausea/vomiting, infections, fatigue, febrile neutropenia, diarrhea, thrombocytopenia, anemia, anorexia, leukopenia, hemorrhage, and hyperglycemia. Conclusion: Decitabine in combination with chemotherapy or molecular therapy has shown efficacious properties in refractory or relapsed AML patients.

BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (BCR-ABL1-like ALL or Ph-like ALL) is a neoplastic proliferation of lymphoblasts that has a gene expression profile similar to that of B-ALL with t(9;22)(q34.1;q11.2) BCR-ABL1, but lacks that gene fusion. It is associated with poor prognosis and is seen in 10%-20% of pediatric cases and 20%-30% of adult cases of ALL. It is included as a provisional entity in the revised 4th edition of the WHO Classification. A variety of different genetic abnormalities are identified in this entity, but they all converge on pathways that are potentially responsive to the addition of targeted therapy to conventional chemotherapy. Thus, it is important to screen for BCR-ABL1-like ALL, particularly in adults and pediatric patients with high-risk clinical features. Here, we provide a brief overview of the genetic profile and clinical features of BCR-ABL1-like ALL and review laboratory methodologies for routine identification of this genetically heterogeneous entity.

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Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific \"founder\" mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP.

BCR-ABL caused by the translocation of t(9,22) with elevated tyrosine-kinase activity could induce leukemia in mice, which established BCR-ABL as the molecular pathogenic event in CML (Chronic myeloid leukemia). In recent years, a variety of tyrosine kinase inhibitors (TKIs) targeting at BCR-ABL specifically and effectively have been developed, which has fundamentally promoted the treatment of CML. However, the efficacy of TKIs was limited by its resistance induced by the development of kinase domain mutations and other mechanisms illustrated. In this review, we summarized BCR-ABL inhibitors approved by Food and Drug Administration (FAD), with the same concerns focus on the resistant mechanisms of BCR-ABL inhibitors and therapeutic resistant strategies.

Whether TLX3 is a predictor of prognosis of pediatric T cell acute lymphocytic leukemia (T-ALL) is controversial, with some studies concluding that it is and others concluding the opposite. Therefore, a systematic review was performed to explore the relationship of TLX3 expression with the prognosis of pediatric T-ALL. The PubMed database, The Cochrane Library, conference proceedings, EMBASE databases, and references of published trials and review articles were searched. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios (HRs) for disease-free survival (DFS) and odds ratios (OR) for 5-year DFS were pooled using the STATA package. Ultimately, six trials involving 515 patients with pediatric T-ALL were analyzed. The pooled HR (1.07 [0.32, 3.56], p = 0.91) for DFS and OR (1.30 [0.52, 3.27], p = 0.57) for 5-year DFS showed that the TLX3-positive group showed no statistically significant difference with the TLX3-negative group. Our results suggested that TLX3 expression is not an indicator for the prognosis of pediatric T-ALL.

Despite increased comprehension of acute myelogenous leukemia (AML) pathogenesis, current treatment strategies have done little to improve upon standard induction chemotherapy to induce long-term remissions. Since the identification of the leukemic stem cell, efforts have been placed on identifying therapeutically actionable pathways that distinguish this increasingly important cellular compartment. With the advent of increased genome sequencing efforts and phenotypic characterization, opportunities for personalized treatment strategies are rapidly emerging. In this review, we highlight recent advances in the understanding of leukemic stem cell biology and their potential for translation into clinically relevant therapeutics. NF-kappa B activation, Bcl-2 expression, oxidative and metabolic state, and epigenetic modifications all bear their own clinical implications. With advancements in genetic, epigenetic, and metabolic profiling, personalized strategies may be feasible in the near future to improve outcomes for AML patients.

In recent years, many studies have shown that the HOX gene family involved in the proliferation, differentiation and maturation of hematopoietic progenitor cells. There is a close relationship between the expression of HOX gene family and acute myeloid leukemia (AML). Most of the HOX genes can promote the proliferation and inhibit the differentiation of the hematopoietic progenitor cells, but the mechanism leading to acute myeloid leukemia remains unknown. This review focuses on the relationship between HOX gene and acute myeloid leukemia and the possible mechanisms leading to acute myeloid leukemia.