American journal of blood research最新文献

{"title":"Effects of transfusion of stored blood in patients with transfusion-dependent thalassemia.","authors":"Usman Naeem,&nbsp;Najma Baseer,&nbsp;Muhammad Tariq Masood Khan,&nbsp;Muhammad Hassan,&nbsp;Muhammad Haris,&nbsp;Yasar Mehmood Yousafzai","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to investigate the hematological and biochemical effects of stored blood transfusion on patients with transfusion-dependent thalassemia (TDT).</p><p><strong>Methods: </strong>In this quasi-experimental study, 20-patients with TDT were enrolled. Each participant received on first visit, freshly collected red cell concentrate (RCC) (<2-days storage) and 15-days later on second visit, 7-days stored blood. Blood samples were obtained immediately before and 24-hours after each transfusion. Differences in the Complete blood counts, bilirubin, LDH, C-Reactive protein, ferritin, and iron levels in the pre- and post-transfusion samples were compared between the first and second transfusion.</p><p><strong>Results: </strong>Fresh blood transfusion resulted in a higher (but non-significant) increase in hemoglobin and other red cell parameters. Notably, a significant increase in white cell counts (WCC) was seen in 7-days stored blood vs fresh blood (1.82×10⁹/l vs 1.01×10⁹/l, P=0.002). No statistically significant difference was found in LDH, direct and indirect bilirubin, creatinine, blood glucose, serum uric acid, serum ferritin, and serum Iron levels. There was a statistically significant rise in C-reactive protein levels in stored (6.43±7.46 mg/dl) versus fresh RCC (1.89±2.38 mg/dl), <i>p</i>-value =0.012.</p><p><strong>Conclusions: </strong>We show that in patients with chronic TDT, an increase in inflammation-associated markers (WCC and CRP) is observed. Further studies to assess the extent and duration of this increase are needed.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 6","pages":"592-599"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784645/pdf/ajbr0011-0592.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39877433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab added to standard chemotherapy and its effect on minimal residual disease during induction in CD20 positive pediatric acute lymphoblastic leukemia: a pilot RCT.","authors":"Aditya Kumar Gupta,&nbsp;Anita Chopra,&nbsp;Jagdish Prasad Meena,&nbsp;Jay Singh,&nbsp;Ravindra Mohan Pandey,&nbsp;Sameer Bakhshi,&nbsp;Rachna Seth","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The use of rituximab in the treatment of pediatric acute lymphoblastic leukemia (ALL) has been evaluated but mostly this has been done in the setting of a relapsed or refractory disease. Addition of rituximab to the initial treatment regimen improves the outcomes in adult CD20 positive ALL. This study was done to study its effect on newly diagnosed CD20 positive pediatric ALL patients. Twenty pediatric patients with CD20 positive ALL were randomly assigned to receive rituximab along with standard-chemotherapy [Intervention-arm (IA)] or standard-chemotherapy alone [Standard-arm (SA)]. The absolute blast count (ABC) on day 8, flowcytometry-MRD levels in the peripheral blood (PB) on day-8, day-15 and in the bone marrow (BM) at end of induction (EOI) were the outcome variables. Baseline characteristics were comparable between the IA (n=10) and SA (n=10). Significantly lower day-8 ABC was seen in the IA (P=0.005). The day-8 PB-MRD showed lower values for the IA but the difference wasn't significant (P=0.22). There was no difference between the IA and SA for day-15 PB-MRD and EOI BM-MRD. There was no difference in the incidence of adverse effects. Rituximab added to standard-chemotherapy lead to lower day-8 ABC and lower day-8 PB-MRD in CD20 positive pediatric ALL patients. Rituximab may be beneficial in pediatric ALL treatment. Studies with larger sample size are needed for more evidence.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 6","pages":"571-579"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784647/pdf/ajbr0011-0571.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39877431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An analysis of hematological, coagulation and biochemical markers in COVID-19 disease and their association with clinical severity and mortality: an Indian outlook.","authors":"Mukta Pujani,&nbsp;Sujata Raychaudhuri,&nbsp;Mitasha Singh,&nbsp;Harnam Kaur,&nbsp;Shivani Agarwal,&nbsp;Manjula Jain,&nbsp;R K Chandoke,&nbsp;Kanika Singh,&nbsp;Dipti Sidam,&nbsp;Varsha Chauhan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The \"cytokine storm\" (CS) in COVID-19 leads to the worst stage of illness which can be controlled only with timely intervention. There is an urgent need to identify laboratory markers of disease progression for optimum allocation of resources in developing countries like India.</p><p><strong>Methods: </strong>A cross-sectional study was conducted on 100 COVID-19 positive patients over two months. The cases were sub-classified based on disease severity into mild to moderate (n=61), severe (n=26) and very severe (n=13) and into survivors (n=85) and non-survivors (n=15) based on survivor status. These patients were tested for hematological parameters (total blood lymphocyte counts, NLR, PLR, platelet indices etc.), coagulation markers (D-dimer, fibrin degradation products (FDP), fibrinogen etc.) and biochemical markers (LDH, ferritin, IL-6, procalcitonin, hs-CRP).</p><p><strong>Results: </strong>Statistically significant differences were observed in hematological variables (ANC, NLR and ESR), coagulation parameters (D-dimer, FDP, fibrinogen and thrombin time) and biochemical markers (LDH, ferritin, IL-6, procalcitonin and hs-CRP) with regard to subcategories based of disease severity as well as survivor status. There was strong correlation between NLR, D-dimer, IL-6, procalcitonin and ferritin. IL-6 emerged as the single best marker of disease severity (AUC: 0.997, P=0.00), however procalcitonin, LDH, D-dimer, FDP and NLR could also predict severe disease with a good sensitivity and specificity.</p><p><strong>Conclusion: </strong>To conclude, study demonstrates a plethora of biomarkers which could be utilized to accurately identify the hyperinflammation and tissue damage reminiscent of cytokine storm in COVID-19 patients so that timely, safe, and effective therapies can be administered to prevent progression and potentially reduce mortality.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 6","pages":"580-591"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784646/pdf/ajbr0011-0580.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39877432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial complex II and V activity is enhanced in pediatric acute myeloid leukemia.","authors":"Shilpi Chaudhary, Shuvadeep Ganguly, Archna Singh, Jayanth Kumar Palanichamy, Anita Chopra, Radhika Bakhshi, Sameer Bakhshi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial bioenergetic alterations are commonly observed metabolic adaptation in malignancies including acute myeloid leukemia (AML). Mitochondrial DNA alterations are well known in pediatric AML with possible prognostic significance; however, mitochondrial complex activity and its impact on disease outcome have not been previously explored. The aim of this study was to evaluate the mitochondrial complex II and complex V activity and its prognostic significance in pediatric AML patients.</p><p><strong>Methods: </strong>Consecutive 82 <i>de novo</i> pediatric (≤18 years) patients with AML were included in the study along with age and sex matched controls. Bone marrow mononuclear cells were isolated from baseline bone marrow samples from all patients and controls. DNA, RNA and proteins were extracted and relative expression of mitochondrial biogenesis genes <i>TFAM</i>, <i>POLG</i>, <i>POLRMT</i> were estimated along with mitochondrial DNA copy number. The mitochondrial complex II and V enzymes were immunocaptured and their activity was measured by substrate specific absorbance change by kinetic ELISA. The mitochondrial complex II and V activity was compared with controls and their association with clinico-pathological features and survival outcome were analysed. Complex activity was also correlated with relative expression of biogenesis genes.</p><p><strong>Results: </strong>The activity of mitochondrial complex II and V were found to be significantly enhanced (P = 0.010 and P = 0.0013 respectively) in pediatric AML patients compared to controls. The activity of mitochondrial complex II and V showed significant positive correlation with relative gene expression of mitochondrial biogenesis genes <i>TFAM</i> (P = 0.001 and P = 0.016 respectively) and <i>POLG</i> (P = 0.005 and P = 0.006 respectively). Neither of the two complex activities showed any significant association with baseline disease demographics or any clinico-pathological feature. Furthermore, the complex II and V activity did not show any impact on event free survival (P = 0.25 and P = 0.24 respectively) and overall survival (P = 0.14 and P = 0.17 respectively) in our cohort.</p><p><strong>Conclusion: </strong>The activity of both mitochondrial complex II and V are significantly elevated in bone marrow mononuclear cells of children with AML compared to controls. The enhanced activity may be related to upregulation of mitochondrial biogenesis genes <i>TFAM</i> and <i>POLG</i>. The enhanced activity of either of the complexes did not impact disease biology or survival outcomes in pediatric AML.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"534-543"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610792/pdf/ajbr0011-0534.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory noncoding RNAs: potential biomarkers and therapeutic targets in acute myeloid leukemia.","authors":"Vivek Kumar Singh, Deepshi Thakral, Ritu Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The noncoding RNAs (ncRNA) comprise a substantial segment of the human transcriptome and have emerged as key elements of cellular homeostasis and disease pathogenesis. Dysregulation of these ncRNAs by alterations in the primary RNA motifs and/or aberrant expression levels is relevant in various diseases, especially cancer. The recent research advances indicate that ncRNAs regulate vital oncogenic processes, including hematopoietic cell differentiation, proliferation, apoptosis, migration, and angiogenesis. The ever-expanding role of ncRNAs in cancer progression and metastasis has sparked interest as potential diagnostic and prognostic biomarkers in acute myeloid leukemia. Moreover, advances in antisense oligonucleotide technologies and pharmacologic discoveries of small molecule inhibitors in targeting RNA structures and RNA-protein complexes have opened newer avenues that may help develop the next generation anti-cancer therapeutics. In this review, we have discussed the role of ncRNA in acute myeloid leukemia and their utility as potential biomarkers and therapeutic targets.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"504-519"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610797/pdf/ajbr0011-0504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human leukocyte antigen (HLA) alleles as predictive factors for benefit from lenalidomide in acute myeloid leukemia (AML).","authors":"Sachin Punatar,&nbsp;Anant Gokarn,&nbsp;Lingaraj Nayak,&nbsp;Avinash Bonda,&nbsp;Sumeet Mirgh,&nbsp;Akanksha Chichra,&nbsp;Meenakshi Singh,&nbsp;Selma D'silva,&nbsp;Navin Khattry","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>Lenalidomide is an active agent in acute myeloid leukemia (AML); response rates are about 15-30%. There are no well-defined predictive factors for benefit from lenalidomide in AML. One of the mechanisms of lenalidomide is natural killer (NK) cell activation; hence human leukocyte antigen (HLA) class I alleles (serving as killer immunoglobulin-like receptor ligands) could play a predictive role. We here evaluate the same when lenalidomide was used as a bridge to transplant.</p><p><strong>Methods: </strong>Consecutive AML patients started on lenalidomide as bridge to transplant between Aug-2013 to Aug-2018 were included in this single centre retrospective analysis. The starting dose and schedule of lenalidomide were at the discretion of the treating clinician. Lenalidomide was scheduled to be stopped about 2-4 weeks prior to planned transplant admission (or was stopped earlier if there was intolerance). For this study, event was defined as progression/relapse while on lenalidomide or within 4 weeks of stopping the drug. The primary endpoint was event free survival (EFS). Those who underwent transplant without an event were censored on the day of transplant. Toxicities and post-transplant outcomes were secondary endpoints.</p><p><strong>Results: </strong>Twelve patients (8 males, median age 29 years) were included. At start of lenalidomide, 7 had complete remission (CR)-1 (measurable residual disease or MRD by flow cytometry was positive in 3, negative in 3, and 1 unknown), 4 CR-2 (all MRD negative) and 1 active disease. In the whole cohort, median EFS was not reached with projected 3 year EFS being 80%. There was a significantly reduced risk of event with HLA A*24 (0% vs 75%, P=0.018) or with HLA B*40 (0% vs 60%, P=0.045). Only 1 patient needed discontinuation due to toxicities (cytopenias). Among patients who underwent transplant, grade II-IV acute graft versus host disease (GVHD) was seen in 83%.</p><p><strong>Conclusions: </strong>This is first study to show that HLA alleles may have a bearing on the effect of lenalidomide in AML and could serve as predictive biomarkers. These findings need to be confirmed in larger prospective studies.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"564-570"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610794/pdf/ajbr0011-0564.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review of epigenetic targets in acute myeloid leukemia.","authors":"Shweta Verma,&nbsp;Himanshu Dhanda,&nbsp;Amitabh Singh,&nbsp;Bhavika Rishi,&nbsp;Pranay Tanwar,&nbsp;Sumita Chaudhry,&nbsp;Fouzia Siraj,&nbsp;Aroonima Misra","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"458-471"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610793/pdf/ajbr0011-0458.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An experience with 124 cases of fanconi anemia: clinical spectrum, hematological parameters and chromosomal breakage analysis.","authors":"Rafia Mahmood,&nbsp;Asad Mahmood,&nbsp;Saleem Ahmed Khan,&nbsp;Raza Jaffar","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Fanconi anemia is an inherited bone marrow failure syndrome characterized by somatic abnormalities and an increased predisposition to malignancies.</p><p><strong>Objective: </strong>To determine the clinical spectrum and evaluate the hematological parameters as well as highlight diagnosis by chromosomal breakage analysis of Fanconi anemia patients.</p><p><strong>Material and methods: </strong>A total of 124 patients were diagnosed as having Fanconi anemia from August 2014 to May 2020 at Armed Forces Institute of Pathology, Rawalpindi, Pakistan. Clinical details, somatic abnormalities, radiological findings, lab parameters and result of chromosomal breakage analysis were noted and analyzed.</p><p><strong>Results: </strong>One hundred and twenty four (14.29%) were diagnosed as having Fanconi anemia (FA) on chromosomal breakage test. Median age was 09 years 06 months. Male to female ratio was 1.9:1. Six of these patients exhibited mosaicism and were classified as FA mosaic. Somatic abnormalities were detected in 74 (59.7%) patients; the most common being skeletal abnormalities and short stature.</p><p><strong>Conclusion: </strong>Chromosomal breakage analysis is a cost-effective method for diagnosis of Fanconi anemia. Early diagnosis is pertinent for proper treatment and long term prognosis.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"498-503"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610795/pdf/ajbr0011-0498.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long term outcome of a patient with relapsed refractory early thymic precursor acute lymphoblastic leukemia treated with daratumumab.","authors":"Sachin Punatar,&nbsp;Anant Gokarn,&nbsp;Lingaraj Nayak,&nbsp;Avinash Bonda,&nbsp;Akanksha Chichra,&nbsp;Sumeet Mirgh,&nbsp;Bhausaheb Bagal,&nbsp;Prashant Tembhare,&nbsp;Papagudi Subramanian,&nbsp;Navin Khattry","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The prognosis of patients with relapsed Early Thymic Precursor acute lymphoblastic leukemia (ETP-ALL) remains poor. Unlike B cell Precursor-ALL (BCP-ALL), there are no approved targeted therapies for ETP-ALL. Recent studies have identified a consistent expression of CD38 on the blasts of patients with T-ALL (both ETP-ALL and non ETP-ALL). Pre-clinical studies indicate that CD38 expression persists on the blasts of T-ALL even after receipt of conventional chemotherapy. These findings make CD38 an attractive targetable surface protein for patients with relapsed refractory T-ALL. We were the first to describe the clinical use of daratumumab in a patient of ETP-ALL, with relapsed disease post allogeneic transplant. We describe here the long term outcome of this patient more than 3 years after starting single agent daratumumab.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"528-533"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610796/pdf/ajbr0011-0528.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.","authors":"Harsh Goel,&nbsp;Ekta Rahul,&nbsp;Ishan Gupta,&nbsp;Anita Chopra,&nbsp;Amar Ranjan,&nbsp;Aditya Kumar Gupta,&nbsp;Jagdish Prasad Meena,&nbsp;Ganesh Kumar Viswanathan,&nbsp;Sameer Bakhshi,&nbsp;Aroonima Misra,&nbsp;Showket Hussain,&nbsp;Ritesh Kumar,&nbsp;Archana Singh,&nbsp;G K Rath,&nbsp;Ashok Sharma,&nbsp;Sandeep Mittan,&nbsp;Pranay Tanwar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7479,"journal":{"name":"American journal of blood research","volume":"11 5","pages":"472-497"},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610791/pdf/ajbr0011-0472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}