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Acute myeloid leukemia (AML) is a heterogenous and challenging hematological malignancy with suboptimal outcomes. The implications of advanced technologies in the genetic characterization of AML have enhanced the understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. A comprehensive study of novel mutations is essential to moderate the complicacies in patient management and achieve optimal outcomes in AML. In this review, we summarized the clinical relevance of important novel mutations, including TET2, ETV6, SATB1, EZH2, PTPN11, and U2AF1 , which impact the prognosis of AML. TET2 mutation can lead to DNA hypermethylation, and gene fusion, and mutation in ETV6 disrupts hematopoietic transcription machinery, SATB1 downregulation aggravates the disease, and EZH2 mutation confers resistance to chemotherapy. PTPN11 mutation influences the RAS-MAPK signaling pathway, and U2AF1 alters the splicing of downstream mRNA. The systemic influence of these mutations has adverse consequences. Therefore, extensive research on novel mutations and their mechanism of action in the pathogenesis of AML is vital. This study lays out the perspective of expanding the apprehension about AML and novel drug targets. The combination of advanced genetic techniques, risk stratification, ongoing improvements, and innovations in treatment strategy will undoubtedly lead to improved survival outcomes in AML., Competing Interests: None., (AJBR Copyright © 2023.)

Background: Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients with very heterogenous patient outcomes. The revised World Health Organization classification of the hematolymphoid tumours, 2022, has incorporated AML with Nucleophosphmin1 ( NPM1 ) and CCAAT/enhancer binding protein-alpha ( CEBPA ) mutations as distinct entities. Despite the existing evidence of the prognostic relevance of FMS-like tyrosine kinase-3 internal tandem duplication ( FLT3-ITD ) in AML, it has not been included in the revised classification., Method: In this prospective study, we determined the prevalence of NPM1, CEBPA, and FLT3 gene mutations in 151 de novo CN-AML adult patients (age ≥18 years) in a tertiary care hospital in north India. Additionally, the prognostic relevance of these mutations was also evaluated., Results: NPM1, FLT3-ITD, and CEBPA mutations were found in 33.11%, 23.84%, and 15.77% of CN-AML patients, respectively. CEBPA mutations were found at 3 domains: transactivation domain 1 (TAD1) in 10 (6.62%), transactivation domain 2 (TAD2) in 5 (3.31%), and basic leucine zipper domain (bZIP) in 11 (7.82%) patients. Patients with NPM1 mutation had better clinical remission rate (CR) (P=0.003), event-free survival (P=0.0014), and overall survival (OS) (P=0.0017). However, FLT3-ITD and CEBPA mutations did not show any association with CR (P=0.404 and 0.92, respectively). Biallelic CEBPA mutations were found in 12 (7.95%) patients and were associated with better OS (P=0.043)., Conclusions: These findings indicate that NPM1 and CEBPA mutations can be precisely used for risk stratification in CN-AML patients., Competing Interests: None., (AJBR Copyright © 2023.)

Background and Aims: The objectives of this study were to investigate the cyto-molecular profile and survival of pediatric acute myeloid leukemia (AML)., Methods: This prospective study was carried out in a tertiary care hospital from October 2018 to December 2020. Karyotype and cytogenetics analyses were done to identify chromosomal aberrations in pediatric AML. The targeted molecular panel utilized the polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), and fragment analysis., Results: A total of 70 patients of AML with aged ≤18 years were enrolled in this study. The cytogenetic analyses revealed abnormal/recurrent cytogenetic abnormalities (CA) in 64.3% of patients and normal cytogenetics (CN) in 35.7% of patients. FAB M2 subtype showed frequent aberrant expression of the CD19 marker. CD7, CD11b, and CD36a were significantly present in the absence of molecular markers. Common chromosomal abnormalities were t(translocation) (8;21) (55%), monosomy/deletion 7 (13%), monosomal karyotype (5%) and complex karyotype (3%). The fusion transcripts RUNX1-RUNX1T1 [t(8;21)] (41%) and CBFB-MYH11 [t(16;16)] (3%) were detected by RT-PCR and FLT3-TKD D835 mutation (1.5%) by allele-specific oligo PCR. Fragment analysis revealed NPM1 (8%) mutation and FLT-ITD (9.5%) mutations. Complete remission was achieved in all evaluable patients. The median follow-up period of our patients was 225 days (IQR 28; 426 days). The median event-free survival (EFS) in all patients was 11.9 months (95% CI, 5-12.6 months). The forty months overall survival probability (pOS) was 58% in all patients., Conclusion: The majority of patients had abnormal/recurrent cytogenetics abnormalities. FAB M2 subtype showed frequent aberrant expression of the CD19. The absence of molecular markers may suggest the presence of CD7, CD11b, and CD36a expression. The overall survival has increased considerably in LMIC., Competing Interests: None., (AJBR Copyright © 2022.)

Background: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm distinguished by extensive clonal expansion of plasma cells in the bone marrow (BM) and peripheral blood (PB). PCL is divided into two subtypes: primary (pPCL) originates de novo without preceding multiple myeloma, while secondary (sPCL) comprises a leukemic modification that occurs as a late manifestation from previous multiple myeloma (MM). pPCL and sPCL are clinically and biologically two different entities. The molecular mechanisms of the development of PCL, either primary or secondary, remain poorly understood. We aim to present 5 years of data on clinical profiles and treatment outcomes of pPCL and sPCL patients treated at our cancer hospital in India and to find a predictive parameter of the development of PCL in cases of MM., Methods: In this study, we retrospectively reviewed and evaluated the clinicopathological features, laboratory parameters, immunophenotypic profile, and patient outcomes of 17 PCL cases diagnosed among 180 plasma cell dyscrasia patients during the study period to establish a correlation between pPCL & sPCL for diagnosis and management of PCL., Results: A total of 17 PCL patients were diagnosed among 180 plasma cell dyscrasia patients during the study period. Among PCL patients, 9 cases had pPCL (52.94% of all PCL patients), and 8 cases had sPCL (47.06% of all PCL patients). Peculiar differences were seen between the two PCL types. Both types of PCL had a younger age at the time of diagnosis, having elevated BM plasma cell infiltration percentage, frequent anemia, thrombocytopenia, elevated beta-2-microglobulin (B2M) levels, raised LDH levels, and positive M-protein in both serum and urine. In addition, SFLC assay and Immunofixation assay showed higher κ and lower λ in pPCL compared with sPCL (P<0.05). Higher Renal insufficiency was also observed in pPCL compared to sPCL (P=0.335). The survival and response to treatment of PCL patients remain considerably poor, sPCL exhibit shorter overall survival (OS) than pPCL with (median 1.75 months vs. 7 months respectively, P=0.1682 ). Plasma cell leukemia (PCL) needs to be diagnosed early and requires prompt initiation of treatment before patients get complications., Conclusion: Our study characterizes the clinical and laboratory features of pPCL and sPCL and may aid physicians in prognosticating the course of disease of their patients. However, future multicentre studies are the need of the hour to develop accurate diagnostic criteria and establish the efficacy of therapeutic regimens., Competing Interests: None., (AJBR Copyright © 2022.)

LGL leukemia is a rare chronic lymphoproliferative disorder of cytotoxic lymphocytes which can be immunophenotypically either T cell or NK cell-derived. According to the World Health Organization classification, it can be divided into three subtypes: chronic T-cell leukemia and chronic natural killer cell lymphocytosis, and aggressive natural killer cell LGL leukemia. Clonal proliferation of large granular lymphocytes can be because of stimulation of various molecular pathways namely JAK-STAT3 pathway, FAS/FAS-L pathway, RAS-RAF-1-MEK1-ERK pathway, PI3K/AKT pathway, NF-KB pathway, and Sphingolipid Rheostat pathways. The most common clinical features presenting with this leukemia are neutropenia, anemia, thrombocytopenia. This leukemia is also associated with various autoimmune conditions. It usually has an indolent course except for the aggressive NK cell LGL leukemia. The cause of death in the indolent cases was mostly due to infectious complications related to the neutropenia associated with the disease. The rarity of the disease coupled with the availability of only a handful of clinical trials has been a hindrance to the development of a specific treatment. Most of the cases are managed with immunomodulators. The advances in the knowledge of molecular pathways associated with the disease have brought few targeted therapies into the limelight. We discuss here the evolution, epidemiology, demographic profile, pathophysiology, differential diagnosis, the available treatment options along with the survival and prognostic variables which may help us in better understanding and better management of the disease and hopefully, paving the way for a targeted clinical approach., Competing Interests: None., (AJBR Copyright © 2022.)

Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal modalities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy., Competing Interests: None., (AJBR Copyright © 2021.)

Granulocyte colony-stimulating factors (G-CSFs) have been used post hematopoietic stem cell transplant (HSCT) for earlier neutrophil engraftment. The use of G-CSFs, and their effect on other post-HSCT outcomes remains debatable. In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane library, Google Scholar, and IndMed using a predefined search strategy. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) reporting data on G-CSF administration post-HSCT, published in the English language from their inception until Jan 31, 2021. The primary outcome of this systematic review and meta-analysis was to evaluate the time to neutrophil engraftment (NE). The secondary outcomes were probability of NE, time to platelet engraftment (PE), the incidence of graft-versus-host disease (GVHD), duration of hospital stay (HS), and overall survival (OS). The review is registered with PROSPERO (CRD42020206989). Fourteen studies were extracted (n=9850), of which five were RCTs, and nine were NRSs. As per Egger's test, publication bias was not present for any outcome. After meta-analysis, we found that the duration of NE favouring G-CSF arm from RCTs was -0.94 days (SMD) [(95% CI: -1.38, -0.51); I 2 =35%], and from NRSs -1.2 days (SMD) [(95% CI: -1.43, -0.96); I 2 =74%]. For the outcome of GVHD, the relative risks (RR) of incidence for chronic GVHD and overall GVHD were not significant for the RCTs, and these were 1.11 (RR) [(95% CI: 1.00, 1.22); I 2 =43%] and 1.10 (RR) [(95% CI: 1.03, 1.18); I 2 =48%], respectively for NRSs. There was no difference in the incidence of GVHD (acute or chronic) in both arms. No significant difference was found between the two arms for the outcomes of PE, HS, and OS. For NE, there was a marginal benefit of around one day with the use of G-CSF. The use of G-CSF did not alter time to PE, the incidence of GVHD, HS, and OS in both arms., Competing Interests: None., (AJBR Copyright © 2021.)

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia., Competing Interests: None., (AJBR Copyright © 2021.)

Introduction: Acute promyelocytic leukemia (APML), although genetically and morphologically distinct from other AML (acute myeloid leukemia) subtypes, is one of the most best responsive acute myeloid leukemia. -Conventional diagnostic methods and morphological hints often fail in the majority of the cases in the peripheral laboratories owing to resource constraints, unavailability of cytogenetic work-up, hypogranular variants, morphological mimicry by AML-monocytic and myelo-monocytic, etc. Flowcytometry (FCM), however, can be utilized as a feasible and reliable immunophenotypic diagnostic and prognostic tool for prompt identification of APML. In order to rapidly and sensitively diagnose APML we intended to suggest a cost effective, sensitive FCM panel and also to prognositicate patients., Material and Methods: In this retrospective study, flowcytometry characteristics of 123 cases of acute promyelocytic leukemia were studied including 40 hypogranular variants. The expression of markers was compared with the Mean flurescent Intensity (MFI) and percent expression of markers. A non-statistical comparison was made with cases of acute monocytic leukemia. The cases were grouped according to their immunophenotype characteristics and expression with comparison of MFI by multivariate logistic regression. The aberrant markers positive at diagnostic and remission flow test were compared with the survival outcomes, and their positive predictive values were calculated., Results: The most common feature of side scatter property was the absence of blasts in the window and high side scatter, except hypogranular variants which had low side scatter. Immunophenotypically characterised by positivity for CD117, cMPO, and bright CD33 and CD13 positivity and lack of CD34 and HLA-DR was seen in the majority of APML including hypo-granular variant. We suggest a rapid diagnostic four-tube panel for fast and rapid diagnosis of APML, including hypogranular variants with 100% sensitivity. The study also identified six groups of immunophenotypes with significant prediction values of APML, including hypogranular variants. The study also highlights CD2, CD56, and CD9 as prognostic markers for acute promyelocytic leukemia., Competing Interests: A retrospective study from 2014-2019 of all the cases of APML after obtaining consent from patients/guardians were evaluated for clinicopathological parameters, flow cytometry, and cytochemistry. Reverse transcriptase PCR (RT-PCR) for PML-RAR alpha was done from private labs by outsourcing in cases with clinical suspicion or where-ever possible. Routine molecular cytogenetic studies for APL specific performed by standard G-banding techniques on unstimulated culture. Inclusion criteriaCases of untreated acute leukemia that attended the OPDs of AIIMS and VMMC and SJH hospital in pediatric OPDs which were diagnosed as APML and decided to continue treatment in the same centre. Cases that had given consent to participate in the study.Exclusion criteriaCases which had been partially treated outside, cases which did not continue treatment at the same centre, cases which showed reactivity to HIV/HCV and HBsAg were excluded from the study. Also, cases in which consent could not be obtained were excluded from study. Four-color FCM analysis was performed for all cases using BD FACS Calibur and BC FC500, and the data were analyzed with FACS DIVA software (BD Biosciences, San Jose, CA) in accordance with the international consensus recommendations on flowcytometric analysis of hematolymphoid neoplasia [5]. The antibodies in our routine panel included shown in Table 1 apart from the screening cytoplasmic tube for the exclusion of lymphoid and other myeloid neoplasms. The gating strategy was followed as published before [6]. The percent positivity taken for the categorization of negative, dim positive, and positive is mentioned in Table 1, along with the clone utilized during the experimentation. For the purpose of comparing our results with the literature, we arbitrarily defined in this study staining of 20% or more positivity for the markers like CD34, HLA-DR, CD33, CD13, etc. The minimum positive blast population and the criterion for dim positivity to be considered as positive being mentioned in the table along with other immunomarkers. We then analyzed the immunophenotypic profiles of these cases in relation to individual antigen expression and karyotype findings. The aberrant markers positive at diagnostic and remission flow test were compared with the survival outcomes, and their positive predictive values were calculated with the ability for the exclusion of other diagnosis from APML by comparing the immunophenotypic results with a different series of AML cases (control for statistical analysis). Clinical management protocol as per NCCN update Version 2.2014 (Annexure 1). Clinical outcomes: As per the standard definitions of CR, OS, RFS, and EFS [2] (Annexure 2), Statistical analysis. Table 1Flow markers with clone and distribution of positivityS No.CD MarkerConjugateCloneMin Positive Population percentDim PositiveMean MFI Normal/Blast1CD34PC5.5Immu13320100.42/0.722CD117PC7104D2D120100.20/0.353HLA-DRPacific blueImmu-35720104.33/0.544CD2ECD39C1.510105.18/1.055CD3APC 750UCHT1101016.77/1.346CD7APC8H8.1101028.63/0.107CD9APC 750ALB615150.46/62.468CD11bAPCBear115158.29/3.309CD11cPC7BU1515150.32/0.7010CD13ECDSJ1D120150.20/9.3411CD14APC 750RMO5220200.31/0.9112CD16FITC3G820200.22/1.0513CD18PE7E420200.68/0.7614CD33APCD3HL60.25120150.40/35.5415CD56PEN90120200.29/0.2216CD64ECD2220200.44/5.4217CD65FITC88H720200.20/0.5618cMPO*FITCCLB-MPO-103200.93/3.67*Any positive percent was reported independently regardless of the threshold.Statistical analysisAnalysis was done on the patients who consented for the study and for treatment. Fisher exact test was used to compare differences between groups with respect to clinicopathological characteristics, clinical outcomes, and response to therapy. The probability of survival was estimated with the use of the Kaplan and Meier method for overall survival, event-free survival and disease-free survival and compared by the log-rank test among risk groups. All survival estimates are reported ± 1 SE. All P values were two-sided, with values of 0.05 or less indicating a statistical significance. All statistical analyses were performed using SPSS v.16.0 software (SPSS Inc., Chicago, USA). Clinical features are presented as percentages (%) for categorical variables and as mean values ± standard deviation (SD) for normally distributed continuous variables. The chi 2 test was used to analyze differences in the distribution of categorical variables between patient subsets. The Chi 2 test was used to detect differences in the distribution of continuous parametric variables. Multivariateanalyses were performed using a multiple logistic regression analysis. P values <0.05 were considered statistically significant. A cutoff of >10% was used to quantify the presence of a subpopulation of CD34+ and CD56+ cells, and a cutoff of >20% was used for defining positivity for CD34, CD33, CD56 as mentioned in Table 1. Table 2Immunophenotypic characteristicsCasesNo.HLA DRCD33CD13CD34#cMPO*CD11b$CD11c@CD117CD9CD56CD2CD15All APL cases12317 (13.8)123 (100)122 (99.1)30 (24.4%)123 (100)2612122 (99.1)120183040Hyper granular variant831283 (100)82 (98.7)15 (18.1)83 (100)18 (21.7)1182 (98.7)80101327Hypo Granular Variant405 (12.5)40 (100)40 (100)15 (37.5)40 (100)8 (20.0)8 (20.0)40 (100)40 (100)8 (20.0)1713AML M4/M560404937545855524201390245#including heterogenous positive population.*Considered positive even if the threshold for 3% population of interest is present.$co-positivity for CD117 required to distinguish maturing myeloid precursors or granular monocytes includes dim positivity.@Indicates positivity if more than 5% of population shows moderate to bright positivityNone., (AJBR Copyright © 2021.)

Introduction: Transfusion is commonly done in clinical indications and complications arising due to Anemia, shock, blood loss, thrombocytopenia due to any cause, ineffective erythropoiesis. Pregnancy is a physiological condition characterized by Anemia, fluid overload, hypercoagulable state, and antifibrinolytic condition, which can cause various reactions that could be anticipated during a blood transfusion. With an aim to understand the effects of transfusions on hematological parameters in pregnancy. The results of whole blood and component transfusion were studied to understand increments and their effects so that rationalized transfusion decisions during pregnancy can be undertaken, considering the physiological changes in pregnancy on hemodynamics are present., Methodology: A prospective study with 80 pregnant females undergoing blood transfusion was studied. Their coagulation and hematological profile were correlated to derive a conclusion for the effect of transfusion of blood and its products., Results: A mean increment of 0.55+0.07 g/dL hemoglobin (Hb) was noted along with a slight increase in RBC count (0.25+0.07 millions/mm 3 ), hematocrit (HCT) (1.9+0.42%), TLC (400+565 cells/mm 3 ). This statistically significant mean increase in hemoglobin, RBC count, and hematocrit was significantly lower than that compared to studies in the west and non-anemic patients. A mean increment of 7.79+1.51 µg/dL (statistically significant) in serum iron was seen. A significant improvement in their coagulation profile was achieved by plasma transfusion (FFP). Clotting time (CT) decreased by a mean value of 196.43+56.69 secs and prothrombin time (PT) by 2.64+0.63 secs (P<0.05). All transfusion reactions in our study were associated with PRBC transfusion, non-hemolytic immunological type, urticarial transfusion reactions (UTR) more common in multiparous women-0.2% in primigravida to 21.7% and 37.5% in 3rd and 4th parity similar to that observed in other studies., Conclusion: Although different researchers have done numerous studies, the physiological profile of pregnant females in India is markedly different in nutritional profile, ethnicity, environmental factors, and background. The availability of tertiary care medical facilities during ANCs is also known to affect pregnancy outcomes and the presentation of patients at term or in labor. The variety of factors affect the baseline hematological status of pregnant females and, hence, post-transfusion hematological factors. These are therefore markedly different from prior published studies. It is concluded that PRBC transfusion in pregnant women causes a lower increase in mean Hb and HCT values than in the west, and ferritin and serum iron are not reliable indicators of Anemia in transfusion. Due to lower increments in all values except platelets could be the reason for this could be contributed by confounding factors like Anemia, hyperfibrinogenemia, volume overload, and ethnicity., Competing Interests: None., (AJBR Copyright © 2021.)

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative neoplasm overlap disease. JMML is associated with mutations in the RAS pathway genes resulting in the myeloid progenitors being sensitive to granulocyte monocyte colony-stimulating factor (GM-CSF). Karyotype abnormalities and additional epigenetic alterations can also be found in JMML. Neurofibromatosis and Noonan's syndrome have a predisposition for JMML. In a few patients, the RAS genes ( NRAS, KRAS , and PTPN11 ) are mutated at the germline and this usually results in a transient myeloproliferative disorder with a good prognosis. JMML with somatic RAS mutation behaves aggressively. JMML presents with cytopenias and leukemic infiltration into organs. The laboratory findings include hyperleukocytosis, monocytosis, increased hemoglobin-F levels, and circulating myeloid precursors. The blast cells in the peripheral blood/bone-marrow aspirate are less than 20% and the absence of the BCR-ABL translocation helps to differentiate from chronic myeloid leukemia. JMML should be differentiated from immunodeficiencies, viral infections, intrauterine infections, hemophagolymphohistiocytosis, other myeloproliferative disorders, and leukemias. Chemotherapy is employed as a bridge to HSCT, except in few with less aggressive disease, in which chemotherapy alone can result in long term remission. Azacitidine has shown promise as a single agent to stabilize the disease. The prognosis of JMML is poor with about 50% of patients surviving after an allogeneic hematopoietic stem cell transplant (HSCT). Allogeneic HSCT is the only known cure for JMML to date. Myeloablative conditioning is most commonly used with graft versus host disease (GVHD) prophylaxis tailored to the aggressiveness of the disease. Relapses are common even after HSCT and a second HSCT can salvage a third of these patients. Novel options in the treatment of JMML e.g., hypomethylating agents, MEK inhibitors, JAK inhibitors, tyrosine kinase inhibitors, etc. are being explored., Competing Interests: AKG has been sanctioned a grant for research on the genomic landscape of JMML from the Indian Council of Medical Research., (AJBR Copyright © 2021.)

The progress in the field of personalized therapy has been the backbone for the improved mortality and morbidity figure in cancer especially with reference to acute leukemia. The same has been supported by evolving research and development in the field of genomics. The newer discoveries of mutations and the account of already discovered mutations have been playing a pivotal role to refine management strategy. Here, in this review, we are giving an account of relevant mutations and their potential role in the pathogenesis of acute leukemia. The article discusses the old and newly discovered mutations in acute myeloid/lymphoblastic leukemia. The various pathways and cross-talks between the mutations have been briefly described to develop insight towards their contributory and consequent role in the neoplastic process. The article is to sensitize the students, clinicians, and researchers towards the recent updates and development in genomics of acute leukemia., Competing Interests: None., (AJBR Copyright © 2021.)

Cancer is a highly proliferative disease, which is caused due to the loss of regulation of cell cycle and apoptosis, DNA damage, faulty repair system etc. The cancer microenvironment plays a pivotal role in disease progression as they contain different types of innate and adaptive immune cells. The most important molecules that establish a correlation between inflammation, innate immunity, adaptive immunity, and cancer are the molecules released by inflammatory cells in cancer microenvironment. These molecules secreted by the immune cells, which might activate a pro-tumorigenic and anti-tumorigenic response in cancer. In inflammatory microenvironment, the equilibrium state of immunosuppressive and immunostimulatory signals are important in tumor suppression. The immunotherapeutic approaches could be more effective in cancer treatment. However, advancement in immunobiology and cancer are improving the prospects of immunotherapy alone and/or in combination with the conventional therapies. Thus, the review attempts to highlight a promising and futuristic immunotherapeutic approach in combination with conventional treatment modalities., Competing Interests: None., (AJBR Copyright © 2020.)

Wilms tumor gene 1 (WT1) is an important gene which is involved in growth and development of many organs. It is identified as a tumor suppressor gene in nephroblastoma. However, its role as a tumor oncogene has been highlighted by many studies in haematological as well as non haematological malignant neoplasm. The expression of WT1 on leukemic blast cells sensitised us to explore its impact on neoplastic phenomenon. WT1 is has been found both mutated as well as over expressed in different subsets of acute myeloid leukemia (AML). WT1 is a gene has been used as a biomarker for diagnosis, monitoring of minimal residual disease (MRD) and detection of relapse for molecular remission in AML. It also has potential of being a predictive molecular predictive biomarker for the treatment of leukemic cases after allogeneic transplantation. The WT1 specific expression on blast cells and its interaction with cytotoxic T cell has also been explored for its potential usage WT1 based immunotherapy. Here, we are reviewing molecular updates of WT1 gene and discuss its potential clinical applications as a predictive molecular biomarker for diagnosis, as MRD detection and as immunotherapy in AML., Competing Interests: None., (AJBR Copyright © 2020.)

Background: The pathogenic role of Wilms tumor 1 gene (WT1) is well known in renal cancer. However, recently, its over expression is been documented in cases of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and myelodysplastic syndrome (MDS). WT1 mutations is found in about 6%-15% of cases of AML affecting mainly hotspot exon 7 and 9, and less frequently in other exon such as 1, 2, 3, and 8. Different studies have shown equivocal findings with few of them depicting poorer prognosis, while others suggesting lack of any significant clinical impact., Objective: This study was planned to evaluate prevalence of WT1 gene mutation on exon 7 & 9 in de novo cases of AML and its correlation with their clinical features and disease course., Methodology: A total of newly diagnosed and treatment naive 100 cases of AML, having blast count of ≥20% in peripheral blood or bone marrow were enrolled. Genomic DNA of all participants was extracted from blood/bone marrow sample using Qiagen ® DNA extraction kit. Haematological workup for counts and flow cytometry based immunophenotypes was done. Mutation on exon 7 & 9 were detected with the help of Sanger sequencing., Results: WT1 mutations were detected in both types of cases having normal vs. abnormal cytogenetics. The overall prevalence of WT1 mutation of 2% was found. We have reported one novel mutation on exon 9 of WT1 gene. Twelve cases (12%) among all analyzed AMLs were found to have synonymous single nucleotide polymorphism (SNPs) on exon 7 which has been previously reported in SNP database (rs16754)., Conclusion: In our study, presence of synonymous SNP was not associated with any change at protein level. We also evaluated mutational status with deaths during induction remission and concluded that presence of WT1 gene mutation was associated with death during induction therapy., Competing Interests: None., (AJBR Copyright © 2020.)

Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. However, the usefulness of ETP-ALL immunophenotype and assessment of ABD for this purpose has been questioned and, MEF2C has not been studied in much detail. In this prospective analysis of 143 T-ALL patients, we evaluated the mutual association of these three entities and also determined how immunophenotypically-defined poor prognosis immature T-ALL relates to these entities. We found that all three of them, especially ABD, nearly completely characterized the immature group. High MEF2C expression reflected ETP-ALL somewhat poorly and a few ABD and MEF2C -high patients had non-immature immunophenotype-findings, that though in accord with published literature, call for exploration per T-cell receptor (TCR) classification scheme. ETP-ALL and MEF2C high but not ABD had a higher frequency of minimal residual disease positivity and poor event-free survival. MEF2C high, not ETP-ALL immunophenotype or ABD, had poorer overall survival. The value of ETP-ALL immunophenotype and MEF2C status, as indicators of poor treatment response, needs further evaluation for possible incorporation in standard T-ALL management practice., Competing Interests: None., (AJBR Copyright © 2020.)