101 results match your criteria Acute Leukemias of Ambiguous Lineage


Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets.

Cancers (Basel) 2022 Apr 8;14(8). Epub 2022 Apr 8.

Hematology and Immunology Section, Department of Medicine and Surgery, CREO, Università degli Studi di Perugia, 06132 Perugia, Italy.

A wide range of immature acute leukemias (AL), ranging from acute myeloid leukemias with minimal differentiation to acute leukemias with an ambiguous lineage, i.e., acute undifferentiated leukemias and mixed phenotype acute leukemia with T- or B-plus myeloid markers, cannot be definitely assigned to a single cell lineage. Read More

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Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

Curr Oncol Rep 2022 Apr 5. Epub 2022 Apr 5.

Faculty of Medicine, Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Sölvegatan 25b, 22185, Lund, Sweden.

Purpose Of Review: Recent advances in the small field of the rare mixed phenotype acute leukemias (MPAL) are presented focusing on a better understanding of their pathophysiology and search for better therapeutic approaches.

Recent Findings: Three aspects of respective classification, therapy, and immunophenotype of MPAL are reviewed. New proposals have been made to segregate MPAL subtypes based on their genomic landscape. Read More

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ZNF384 Fusion Oncoproteins Drive Lineage Aberrancy in Acute Leukemia.

Blood Cancer Discov 2022 05;3(3):240-263

Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.

ZNF384-rearranged fusion oncoproteins (FO) define a subset of lineage ambiguous leukemias, but their mechanistic role in leukemogenesis and lineage ambiguity is poorly understood. Using viral expression in mouse and human hematopoietic stem and progenitor cells (HSPC) and a Ep300::Znf384 knockin mouse model, we show that ZNF384 FO promote hematopoietic expansion, myeloid lineage skewing, and self-renewal. In mouse HSPCs, concomitant lesions, such as NRASG12D, were required for fully penetrant leukemia, whereas in human HSPCs, expression of ZNF384 FO drove B/myeloid leukemia, with sensitivity of a ZNF384-rearranged xenograft to FLT3 inhibition in vivo. Read More

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Incidence of myeloid neoplasms in Spain (2002-2013): a population-based study of the Spanish network of cancer registries.

Sci Rep 2022 01 10;12(1):323. Epub 2022 Jan 10.

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Comprehensive population-based data on myeloid neoplasms (MNs) are limited, mainly because some subtypes were not recognized as hematological cancers prior to the WHO publication in 2001, and others are too rare to allow robust estimates within regional studies. Herein, we provide incidence data of the whole spectrum of MNs in Spain during 2002-2013 using harmonized data from 13 population-based cancer registries. Cases (n = 17,522) were grouped following the HAEMACARE groupings and 2013-European standardized incidence rates (ASR), incidence trends, and estimates for 2021 were calculated. Read More

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January 2022

The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage.

Sci Rep 2021 12 21;11(1):24290. Epub 2021 Dec 21.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave., Wuhan, 430030, People's Republic of China.

Acute leukemia with ambiguous lineage (ALAL) is a rare and highly aggressive malignancy with limited molecular characterization and therapeutic recommendations. In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018. The diagnose of ALAL was based on either EGIL or 2016 WHO criteria, a total of 39 patients were included. Read More

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December 2021

Redefining the biological basis of lineage-ambiguous leukemia through genomics: BCL11B deregulation in acute leukemias of ambiguous lineage.

Best Pract Res Clin Haematol 2021 12 23;34(4):101329. Epub 2021 Oct 23.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address:

Acute leukemias of ambiguous lineage (ALAL), including mixed phenotype acute leukemia (MPAL) and related entities such as early T-cell precursor acute leukemia (ETP-ALL), remain diagnostic and clinical challenges due to limited understanding of pathogenesis, reliance of immunophenotyping to classify disease, and the lack of a rational approach to guide selection of appropriate therapy. Recent studies utilizing genomic sequencing and complementary approaches have provided key insights that are changing the way in which such leukemias are classified, and potentially, treated. Several recurrent genomic alterations define leukemias that straddle immunophenotypic entities, such as ZNF384-rearranged childhood B-ALL and B/myeloid MPAL, and BCL11B-rearranged T/myeloid MPAL, ETP-ALL and AML. Read More

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December 2021

Enrichment of Double RUNX1 Mutations in Acute Leukemias of Ambiguous Lineage.

Front Oncol 2021 31;11:726637. Epub 2021 Aug 31.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. Read More

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Efficacy of combination of venetoclax with azacitidine or chemotherapy in refractory/relapse acute leukemias of ambiguous lineage, not otherwise specified.

Exp Hematol Oncol 2021 Sep 16;10(1):46. Epub 2021 Sep 16.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

Acute leukemias of ambiguous lineage, not otherwise specified (ALAL-NOS) is a rare type of acute leukemia. Management of relapse/refractory (R/R) patients is still challenging.traditional chemotherapy treatment is not effective. Read More

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September 2021

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria.

Zhongguo Dang Dai Er Ke Za Zhi 2021 Aug;23(8):835-840

Department of Hematology and Oncology/Ministry of Education Key Laboratory of Child Development and Disorders/National Clinical Research Center for Child Health and Disorders/China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Children's Hospital of Chongqing Medical University/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

Objectives: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria.

Methods: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. Read More

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Update on Acute Leukemias of Ambiguous Lineage.

Clin Lab Med 2021 09 2;41(3):453-466. Epub 2021 Jul 2.

Department of Pathology, University of Texas Southwestern, Texas, BioCenter, 2230 Inwood Road, EB03.220G, Dallas, TX 75235, USA.

Acute leukemias of ambiguous lineage are a heterogenous group of diseases that include acute undifferentiated leukemias and mixed-phenotype acute leukemias (MPALs). These leukemias pose a challenge for pathologists and clinicians alike in diagnosis, treatment, and further management. Recent genetic characterization has provided insights into their underlying biology and classification, and has offered potential for targeted therapies. Read More

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September 2021

Enhancer Hijacking Drives Oncogenic Expression in Lineage-Ambiguous Stem Cell Leukemia.

Cancer Discov 2021 11 8;11(11):2846-2867. Epub 2021 Jun 8.

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.

Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of , a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to . Read More

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November 2021

[The pathological diagnosis and differential diagnosis of hematopoietic cell tumors of ambiguous lineage].

Zhonghua Xue Ye Xue Za Zhi 2021 Mar;42(3):238-242

Department of Pathology, Third Hospital, School of Basic Medical Sciences, Peking University, Beijing 100191, China Beijing Boren Hospital, Beijing 100070, China.

To explore the key points of the pathological and differential diagnoses of extra-medullary masses of hematopoietic cell tumors of ambiguous lineage, and to discuss the possible solutions. Five hematopoietic cell tumors of ambiguous lineage cases were collected, including myeloid sarcoma, mixed phenotype acute leukemia, B/myeloid, T-lymphoblastic lymphoma combined with acute myeloid leukemia, acute undifferentiated leukemia with cutaneous MPDCP and early T-precursor cell acute lymphoblastic leukemia. The data including morphology, immunostaining, and flow cytometry analysis were collected, and we explored the problems and differential diagnosis in the diagnosis of hematopoietic cell tumors of ambiguous lineage. Read More

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14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia.

Blood 2021 09;138(9):773-784

Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

Acute leukemias (ALs) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by coexpression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML, M0 or M1), T/myeloid mixed-phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. Read More

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September 2021

Diagnosis of rare subtypes of acute myeloid leukaemia and related neoplasms.

Pathology 2021 Apr 4;53(3):312-327. Epub 2021 Mar 4.

Clinical Haematology, Peter MacCallum Cancer Centre, The Royal Melbourne Hospital, Melbourne, Vic, Australia.

The diagnosis of acute myeloid leukaemia and related neoplasms in adults is challenging as this requires the integration of clinical findings, morphology, immunophenotype, cytogenetics, and molecular genetic findings. Lack of familiarity with rare subtypes of acute leukaemia hinders the diagnosis. In this review, we will describe diagnostic findings of several rare acute myeloid leukaemias and related neoplasms that primarily occur in adults including information on presentation, morphology, immunophenotype, genetics, differential diagnosis, and prognosis. Read More

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Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group.

Mod Pathol 2021 07 1;34(7):1358-1366. Epub 2021 Feb 1.

Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. Read More

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Red Plaques in a Pediatric Patient With Acute Leukemia of Ambiguous Lineage.

JAMA Oncol 2021 03;7(3):454-455

SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, South Australia, Australia.

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Diagnostic approach to the evaluation of myeloid malignancies following CAR T-cell therapy in B-cell acute lymphoblastic leukemia.

J Immunother Cancer 2020 11;8(2)

Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

Immunotherapeutic strategies targeting B-cell acute lymphoblastic leukemia (B-ALL) effectively induce remission; however, disease recurrence remains a challenge. Due to the potential for antigen loss, antigen diminution, lineage switch or development of a secondary or treatment-related malignancy, the phenotype and manifestation of subsequent leukemia may be elusive. We report on two patients with multiply relapsed/refractory B-ALL who, following chimeric antigen receptor T-cell therapy, developed myeloid malignancies. Read More

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November 2020

Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study.

Ann Hematol 2020 Sep 17;99(9):2119-2124. Epub 2020 Jul 17.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Read More

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September 2020

Toxicity Profile of PEG-Asparaginase in Adult Patients With Acute Lymphoblastic Leukemia in Brazil: A Multicenter Cross-Sectional Study.

Clin Lymphoma Myeloma Leuk 2020 08 13;20(8):e523-e528. Epub 2020 Apr 13.

Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.

Background: Currently, pediatric-inspired regimens are commonly applied to adults with acute lymphoblastic leukemia (ALL) after the recent recognition that these protocols improve survival. While asparaginase in whatever available formulation is a key component of modern treatment of ALL, many adult oncologists and hematologists struggle to deal with its particular toxicities in clinical practice. We reviewed toxicity outcomes of pegylated asparaginase (PEG-ASP) in adults with ALL treated in 3 reference centers in Brazil. Read More

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Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study.

Lancet Oncol 2020 04 11;21(4):551-560. Epub 2020 Mar 11.

Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. Electronic address:

Background: Outcomes for children with relapsed or refractory acute myeloid leukaemia remain poor. The BCL-2 inhibitor, venetoclax, has shown promising activity in combination with hypomethylating agents and low-dose cytarabine in older adults for whom chemotherapy is not suitable with newly diagnosed acute myeloid leukaemia. We aimed to determine the safety and explore the activity of venetoclax in combination with standard and high-dose chemotherapy in paediatric patients with relapsed or refractory acute myeloid leukaemia. Read More

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Diagnostic workup of acute leukemias of ambiguous lineage.

Am J Hematol 2020 06 19;95(6):718-722. Epub 2020 Mar 19.

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.

Acute leukemias of ambiguous lineage (ALAL) comprise acute undifferentiated leukemias (AUL) and mixed-phenotype acute leukemias (MPAL). In the revised fourth edition of the World Health Organization (WHO) classification provided further refinements to the diagnostic criteria for ALAL. Molecular characterization of MPALs using comprehensive next-generation sequencing (NGS) has provided insights into their underlying biology and enabled a deeper understanding of ALAL classification. Read More

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Molecular Complete Remission Following Ivosidenib in a Patient With an Acute Undifferentiated Leukemia.

J Natl Compr Canc Netw 2020 01;18(1):6-10

Division of Hematology, Department of Internal Medicine, and.

Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia-like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Read More

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January 2020

Refined Disease Risk Index for Hematological Malignancies, Including Rare Disorders, After Allogeneic Stem Cell Transplantation.

Transplant Proc 2019 Dec 14;51(10):3437-3443. Epub 2019 Nov 14.

Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Objective: The refined disease risk index (R-DRI) is a well-designed prognostic parameter that is based on only the disease type and status and is used for stratifying patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT) into 4 risk groups. However, the application of the R-DRI for rare diseases has remained unclear.

Methods: We evaluated 135 patients who underwent allo HSCT for hematological malignancies including rare diseases, such as acute leukemia of ambiguous lineage, acute T-cell leukemia/lymphoma, extranodal natural killer T-cell lymphoma, and lymphoblastic lymphoma, at our institute. Read More

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December 2019

Mixed-phenotype acute leukemia: A cohort and consensus research strategy from the Children's Oncology Group Acute Leukemia of Ambiguous Lineage Task Force.

Cancer 2020 02 29;126(3):593-601. Epub 2019 Oct 29.

Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory University, Atlanta, Georgia.

Background: Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.

Methods: To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Read More

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February 2020

Multiparametric Flow Cytometry in Mixed Phenotype Acute Leukemia.

Indian J Hematol Blood Transfus 2019 Jul 13;35(3):451-458. Epub 2019 Feb 13.

3Department of Medical Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.

Mixed phenotype acute leukaemia (MPAL) is a diverse group of leukemia of ambiguous lineage diagnosed when blasts in peripheral blood and/or bone marrow have antigens of more than one lineage or a mosaic of blasts belonging to more than one lineage. Retrospective analysis of 218 consecutive cases of acute leukaemia diagnosed by multiparametric flow cytometry (FCM) was done. MPAL cases were identified in accordance with European Group for the Immunological Classification of Leukaemias Criteria and World Health Organization 2008/2016 guidelines for lineage assignment. Read More

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Genetic Testing in the Diagnosis and Biology of Acute Leukemia.

Am J Clin Pathol 2019 08;152(3):322-346

Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis.

Objectives: The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology examined the role of molecular genetics in the diagnosis and biology of acute leukemia.

Methods: Acute leukemias were reviewed in two sessions: "Genetic Testing in Diagnosis of Acute Leukemias" (53 cases) and "Genetics Revealing the Biology of Acute Leukemias" (41 cases).

Results: Cases included acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemia of ambiguous lineage. Read More

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Acute Leukemias of Ambiguous Lineage: Clarification on Lineage Specificity.

Surg Pathol Clin 2019 Sep;12(3):687-697

Department of Pathology, Boston Children's Hospital, BCH 3027, 300 Longwood Avenue Bader 126.2, Boston, MA 02115, USA.

Acute leukemias of ambiguous lineage (ALAL) include acute undifferentiated leukemia and mixed-phenotype acute leukemia (MPAL). This article provides an overview of the diagnosis of ALAL and focuses on the data accounting for the current lineage-assignment criteria for blasts harboring more than one lineage-associated marker. In addition, the currently known molecular data are reviewed, which show that MPAL-associated gene mutations, methylation signatures, and expression profiles are a mixture of those seen in both acute myeloid leukemia and acute lymphoblastic leukemia. Read More

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September 2019

Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL.

Arch Physiol Biochem 2021 Jun 22;127(3):285-289. Epub 2019 Jul 22.

HSCT Research Center, Laboratory Hematology and Blood Banking Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

B-lineage acute lymphoblastic leukemia (B-ALL) is the most common acute leukemia in childhood and adults, which caused by many various crystalline and unclear agents. Owning to this matter, no significant progress has been made in the patients-recovery. Recently, autophagy pathway is considered as an ambiguous agent in leukemia evaluation. Read More

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