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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.

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.

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

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.

Background: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma seen in immunocompromised individuals. It has a diffuse growth pattern, with no standard therapy and a poor survival rate. Due to overlap in presenting features with lymphoma and myeloma, PBL is often a diagnostic dilemma. We present a case of PBL in a young immunocompetent female who developed treatment associated complications. Case report: A 36-year-old presented with a lesion extending from the oral cavity to the pharynx and involving the angle of the mandible. Radiology and laryngoscopy described a growth pattern that was diagnosed to be PBL on histopathology. The patient underwent chemotherapy using level II DA-EPOCH (dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and prophylactic granulocyte-colony stimulating factor along with radiotherapy and ultimately, achieved metabolic response. However, she developed several episodes of paralytic ileus, cytopenia, oral ulcers, dermatitis and long-standing hypothyroidism as therapy-related complications and has been on treatment for the same ever since. Conclusions: Thus, a high index of suspicion is necessary for early diagnosis and rapid initiation of therapy. Further, there is a need to detect and address therapy related complications early to prevent long-standing, therapy-related side effects from developing and deteriorating the patient’s quality of life.

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.