Mpal

INTRODUCTION: Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation. METHODS: Institutional Review Board (IRB) approval was obtained...

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), mixed phenotypic acute leukemia (MPAL), and acute myeloid leukemia with minimal differentiation (AML-M0) all originate from immature hematopoietic progenitor cells and have a poor prognosis. We investigated the clinical characteristics of these immature leukemias in 17 children (ETP-ALL: 8, MPAL: 5, AML-M0: 4) at seven institutions. Clinical and laboratory findings were comparable across disease types. Eleven and six patients received ALL- and AML-oriented induction chemotherapy, with six and four achieving complete remission (CR), respectively...

BACKGROUND AND AIMS: A recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection. METHODS: We conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls...

Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL's clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later...

BCR::ABL1 fusion is found in < 1% of de novo acute myeloid leukemia (AML) cases and confers a poor prognosis. This Japanese nationwide survey analyzed patients with AML ( n  = 22) and mixed phenotype acute leukemia (MPAL) ( n  = 10) with t(9;22) or BCR::ABL1 who underwent allogeneic hematopoietic cell transplantation (allo-HCT) between 2002 and 2018. The 3-year overall survival (OS) rates were 81.3% and 56.0%, respectively ( p  = 0.15), and leukemia-free survival (LFS) rates were 76...

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is characterized by highly genetic heterogeneity, owing to recurrent fusion genes, gene mutations, intragenic deletion, and gene overexpression, which poses significant challenges in clinical detection. RNA sequencing (RNA-seq) is a powerful tool for detecting multiple genetic abnormalities, especially cryptic gene rearrangements, in a single test. METHODS: Sixty samples (B-ALL, n = 49; T-ALL, n = 9; mixed phenotype acute leukemia (MPAL), n = 2) and 20 controls were analyzed by targeted RNA-seq panel of 507 genes developed by our lab...

OBJECTIVES: Mixed-phenotype acute leukemia (MPAL) is a rare disease associated with difficulties in the correct lineage assignment of leukemic cells. One of the least common subtypes within this category is characterized by the simultaneous presence of B- and T-lineage-defining antigens. Each case of suspected B/T MPAL should be considered in light of all available laboratory and clinical data to avoid misdiagnosis. METHODS: In this study, we describe 6 pediatric patients who presented with leukemic blasts bearing B- and T-lineage antigens at diagnosis, including their clinical, immunophenotypic, morphologic, and cytogenetic characteristics...

MLLT10 fusion is a rare but recurrent genetic driver in acute leukemias. To better understand the genomic landscape of PICALM::MLLT10 (PM) positive acute leukemia, we performed genomic profiling and gene expression profiling in twenty PM-positive patients, including AML (n = 10), T-ALL/LLy (n = 8), Mixed-phenotype acute leukemia (MPAL), T/B (n = 1) and acute undifferentiated leukemia (AUL) (n = 1). Besides confirming the known activation of HOXA, differential gene expression analysis compared to hematopoietic stem cells demonstrated the enrichment of genes associated with cell proliferation-related pathways and relatively high expression of XPO1 in PM-AML and PM-T-ALL/LLy...

While our understanding of the molecular basis of mixed phenotype acute leukemia (MPAL) has progressed over the decades, our knowledge is limited and the prognosis remains poor. Investigating cases of familial leukemia can provide insights into the role of genetic and environmental factors in leukemogenesis. Although familial cases and associated mutations have been identified in some leukemias, familial occurrence of MPAL has never been reported. Here, we report the first cases of MPAL in a family. A 68-year-old woman was diagnosed with MPAL and received haploidentical stem cell transplantation from her 44-year-old son...

T/myeloid mixed phenotype acute leukaemia (MPAL) is a rare aggressive acute leukaemia with poorly understood pathogenesis. Herein, we report two cases of T/myeloid MPAL harbouring BCL11B-associated structural variants that activate TLX3 (TLX3::BCL11B-TLX3-activation) by genome sequencing and transcriptomic analyses. Both patients were young males with extramedullary involvement. Cooperative gene alterations characteristic of T/myeloid MPAL and T-lymphoblastic leukaemia (T-ALL) were detected. Both patients achieved initial remission following lineage-matched ALL-based therapy with one patient requiring a lineage-switched myeloid-based therapy...

t(1;19)(q23;p13) is one of the most common translocation genes in childhood acute lymphoblastic leukemia (ALL) and is also present in acute myeloid leukemia (AML) and mixed-phenotype acute leukemia (MPAL). This translocation results in the formation of the oncogenic E2A-PBX1 fusion protein, which contains a trans-activating domain from E2A and a DNA-binding homologous domain from PBX1. Despite its clear oncogenic potential, the pathogenesis of E2A-PBX1 fusion protein is not fully understood (especially in leukemias other than ALL), and effective targeted clinical therapies have not been developed...

B/T mixed phenotype acute leukemia (MPAL), which represents only 2-3% of all MPAL cases, is classified as a high-risk leukemia subtype. Adults diagnosed with B/T MPAL have a notably low 3-year survival rate, estimated at 20-40%. The rarity and undercharacterization of B/T MPAL present substantial challenges in identifying an optimal treatment protocol. This report aims to shed light on this issue by presenting a case in which a patient with a complex karyotype was treated using a combination of venetoclax, azacitidine, and blinatumomab...

BACKGROUND: : Acute leukemia of ambiguous lineage (ALAL) is a heterogeneous group of rare leukemias that lacks definite evidence of differentiation along one lineage. It includes acute undifferentiated leukemia and mixed-phenotype acute Leukaemia (MPAL). AIMS: The present study highlighted the clinicohematological and immunophenotypic profile of ALAL cases diagnosed in the tertiary care centre of western India. STUDY DESIGN: Retrospective observational study...

B/T mixed phenotype acute leukemia (MPAL) is a rare aggressive leukemia. Three cases of B/T MPAL were identified with comprehensive immunophenotypic, cytogenetic, and molecular studies. T-lineage predominant B/T MPAL shares a genetic signature with T-ALL whereas B/T lineage co-dominant B/T MPAL lacks such a T-ALL signature . All three patients were treated with lineage-matched-ALL therapy and alive at the last follow-up. Our study is the first to demonstrate molecular heterogeneity within B/T MPAL in a context of an immunophenotype of T-lineage versus B-lineage predominance...

Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states...

AIM: The aim was to compare and evaluate the variation in the mandible's posterior anatomic limits (MPAL) stratified by different third molar impaction patterns utilizing cone-beam CT (CBCT) in individuals with skeletal Class III malocclusion. METHODOLOGY: The sample consisted of CBCT records of 80 samples of Class III patients categorized based on the pattern of their third molar impaction. The shortest linear distances from the distal root of the second mandibular molar to the inner cortex of the mandibular body were measured at the crown level, at the cementoenamel junction (CEJ), and at the depths of 4, 6, and 8mm from the CEJ, all parallel to the posterior occlusal line...

Adult B-lineage acute lymphoblastic leukemia (B-ALL) with t(4;11)(q21;q23) is very rare. It is characterized by mixed-lineage leukemia and has the potential for lineage switching during the treatment course. We report the disease course of a patient with B-ALL with t(4;11)(q21;q23) to demonstrate that close monitoring of cell morphology and immunophenotyping is necessary to capture the lineage switch at an early stage. Cell morphology, immunophenotyping, and cytogenetics were used to evaluate the patient's disease status...

Mixed-phenotype acute leukemias (MPAL) account for < 4% of all cases of acute leukemias. These are a heterogeneous group of leukemias grouped together by the WHO classification as "rare subtypes." The diagnosis and treatment of MPAL is extremely challenging particularly for low middle income countries. Of these, B/myeloid and T/myeloid combinations are relatively common subtypes. However, megakaryoblastic and erythroid lineages in combination with other lineages are still rare enough to not even be addressed in the WHO classification...

BACKGROUND/AIM: Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients. PATIENTS AND METHODS: Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization...

RATIONALE: Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous type of leukemia known for its poor prognosis. The optimal treatment strategy for this condition currently lacks consensus, leaving uncertainty in its management. Nonetheless, a potential therapeutic option for patients with refractory MPAL who express target antigens is donor-derived chimeric antigen receptor T (CAR-T) cell therapy. PATIENT CONCERNS: We recently reported a 61-year-old woman with MPAL and elucidated its diagnosis and treatment...