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Transplant Cell Ther 2021 Apr 9. Epub 2021 Apr 9.

RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russian Federation. Electronic address:

Background: The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10-15% of patients are cured by the procedure. Preclinical studies indicate that substitution of posttransplantation cyclophosphomide (PTCY) with bendamustine (PTB) in a prophylaxis regimen may be associated with augmented graft-versus-leukemia (GVL) reaction. Read More

Cell Death Dis 2021 Apr 6;12(4):371. Epub 2021 Apr 6.

Department of Genetics, Federal University of Pernambuco, Recife, Brazil.

Although the mixed lineage leukemia 5 (MLL5) gene has prognostic implications in acute promyelocyte leukemia (APL), the underlying mechanism remains to be elucidated. Here, we demonstrate the critical role exerted by MLL5 in APL regarding cell proliferation and resistance to drug-induced apoptosis, through mtROS regulation. Additionally, MLL5 overexpression increased the responsiveness of APL leukemic cells to all-trans retinoic acid (ATRA)-induced differentiation, via regulation of the epigenetic modifiers SETD7 and LSD1. Read More

Antioxidants (Basel) 2021 Mar 23;10(3). Epub 2021 Mar 23.

University of Tours EA 7501, CNRS ERL 7001, LNOx Team, F-37032 Tours, France.

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Read More

Cancers (Basel) 2021 Mar 20;13(6). Epub 2021 Mar 20.

Department of Pediatric Hematology and Oncology, Clinic of Pediatrics III, University Hospital Essen, 45147 Essen, Germany.

Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited options considering the heavy but unsuccessful pretreatments in these patients. For relapsed/refractory (R/R) patients, hematopoietic stem cell transplantation (HSCT) following ablative chemotherapy presents the only opportunity to cure AML. Read More

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Laboratory of Cytometry, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.

Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. Read More

Front Oncol 2021 16;11:614420. Epub 2021 Mar 16.

Department of Hematology, Children's Hospital of Soochow University, Suzhou, China.

Background: Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients. Read More

Biomed Res Int 2021 11;2021:6643948. Epub 2021 Mar 11.

Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objective: AML is a heterogeneous disease both in genomic and proteomic backgrounds, and variable outcomes may appear in the same cytogenetic risk group. Therefore, it is still necessary to identify new antigens that contribute to diagnostic information and to refine the current risk stratification.

Methods: The expression of C-type lectin-like molecule-1 (CLL-1) in AML blasts was examined in 52 patients with newly diagnosed or relapsed/refractory AML and was compared with two other classic markers CD33 and CD34 in AML, in order to assess the value of CLL-1 as an independent biomarker or in combination with other markers for diagnosis in AML. Read More

Front Oncol 2021 11;11:617937. Epub 2021 Mar 11.

Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Colima, Mexico.

Glucocorticoids (GCs) are a central component of multi-drug treatment protocols against T and B acute lymphoblastic leukemia (ALL), which are used intensively during the remission induction to rapidly eliminate the leukemic blasts. The primary response to GCs predicts the overall response to treatment and clinical outcome. In this review, we have critically analyzed the available data on the effects of GCs on sensitive and resistant leukemic cells, in order to reveal the mechanisms of GC resistance and how these mechanisms may determine a poor outcome in ALL. Read More

Blood Cells Mol Dis 2021 Mar 16;89:102562. Epub 2021 Mar 16.

Laboratory Oncology Unit, Dr. BRAIRCH, AIIMS, New Delhi, India. Electronic address:

Objectives: The treatment of pediatric acute lymphoblastic leukemias (ALL) has seen remarkable advances recently. However, relapse occurs in approximately 20% of cases which necessitates identifying additional high risk parameters for treatment intensification. The aim of this study is to assess the prognostic significance of CD45 antigen expression in pediatric ALL. Read More

J Biochem Mol Toxicol 2021 Mar 22:e22759. Epub 2021 Mar 22.

Department of Oncology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

Leukemia is a malignant tissue-forming disease, which induces the overproduction of large numbers of immature blood cells entering the peripheral blood. It is well documented that inflammation plays a crucial role in the expansion of leukemia. Daphnetin has confirmed anti-inflammatory effects against various diseases. Read More

Front Oncol 2021 4;11:626018. Epub 2021 Mar 4.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn't been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. Read More

Immunity 2021 Mar 15. Epub 2021 Mar 15.

Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC H3C 3J7, Canada; Department of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada. Electronic address:

Acute myeloid leukemia (AML) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Using an original proteogenomic approach, we analyzed the major histocompatibility complex class I (MHC class I)-associated immunopeptidome of 19 primary AML samples and identified 58 tumor-specific antigens (TSAs). These TSAs bore no mutations and derived mainly (86%) from supposedly non-coding genomic regions. Read More

Blood 2021 Mar 15. Epub 2021 Mar 15.

Baylor College of Medicine, Houston, Texas, United States.

The prognosis of patients with acute myeloid leukemia (AML) remains dismal highlighting the need for novel innovative treatment strategies. The application of chimeric antigen receptor (CAR) T-cell therapy to AML patients has been limited in particular by the lack of a tumor-specific target antigen. CD70 is a promising antigen to target AML as it is expressed on the majority of leukemic blasts, whereas little or no expression is detectable in normal bone marrow samples. Read More

Ann Hematol 2021 Mar 2. Epub 2021 Mar 2.

Institute of Medical Genetics and Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031, Basel, Switzerland.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Read More

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan.

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g. Read More

Hematology 2021 Dec;26(1):256-260

Department of Hematology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

is one of the most frequently mutated genes in acute myelogenous leukemia (AML) and the mutation is associated with poor prognosis of patients. Two distinct types of activating mutations have been identified in AML samples. One is internal tandem duplications in the juxtamembrane domain (-ITD) and the other is point mutations in the tyrosine kinase domain (-TKD). Read More

Curr Hematol Malig Rep 2021 Feb 25. Epub 2021 Feb 25.

Department of Leukemia, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA.

Purpose Of Review: The advent of several targeted agents has revolutionized the treatment of acute myeloid leukemia (AML) in recent times; however, majority of patients are still not cured. In the ongoing quest for rationally targeted treatment strategies in AML, scientific endeavors have focused on identifying new antigen targets on the leukemic cells for therapeutic exploitation including strategies to directly deliver toxins into the leukemic blasts as well as strategies that harness host immunity to favorably impact clinical outcomes. Gemtuzumab ozogamicin, a CD33 directed antibody-drug conjugate, has provided the proof of concept for the potential efficacy of monoclonal antibody-based therapies in AML. Read More

Leukemia 2021 Feb 23. Epub 2021 Feb 23.

Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Infants with KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL) have a poor prognosis. KMT2A-r ALL overexpresses FLT3, and the FLT3 inhibitor (FLT3i) lestaurtinib potentiates chemotherapy-induced cytotoxicity in preclinical models. Children's Oncology Group (COG) AALL0631 tested whether adding lestaurtinib to post-induction chemotherapy improved event-free survival (EFS). Read More

Front Oncol 2020 5;10:621458. Epub 2021 Feb 5.

National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.

Metabolism in acute myeloid leukemia (AML) cells is dependent primarily on oxidative phosphorylation. However, in order to sustain their high proliferation rate and metabolic demand, leukemic blasts use a number of metabolic strategies, including glycolytic metabolism. Understanding whether monocarboxylate transporters MCT1 and MCT4, which remove the excess of lactate produced by cancer cells, represent new hematological targets, and whether their respective inhibitors, AR-C155858 and syrosingopine, can be useful in leukemia therapy, may reveal a novel treatment strategy for patients with AML. Read More

Clin Cancer Res 2021 Feb 18. Epub 2021 Feb 18.

Cleveland Clinic, Cleveland, Ohio.

Purpose: We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784).

Patients And Methods: Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin ( = 164) or SC ( = 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs. Read More

EMBO Mol Med 2021 Mar 8;13(3):e12670. Epub 2021 Feb 8.

The Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Altered capacity for self-renewal and differentiation is a hallmark of cancer, and many tumors are composed of cells with a developmentally immature phenotype. Among the malignancies where processes that govern cell fate decisions have been studied most extensively is acute myeloid leukemia (AML), a disease characterized by the presence of large numbers of "blasts" that resemble myeloid progenitors. Classically, the defining properties of AML cells were said to be aberrant self-renewal and a block of differentiation, and the term "differentiation therapy" was coined to describe drugs that promote the maturation of leukemic blasts. Read More

Evid Based Complement Alternat Med 2020 11;2020:4736206. Epub 2020 Dec 11.

Grupo de Inmunobiología y Biología Celular, Unidad de Investigación en Ciencias Biomédicas, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.

The need for new therapeutic approaches to improve the response in acute leukemia (AL), either by directing therapy or with new therapeutic alternatives, has been a research and clinical interest topic. We evaluated whether blasts from AL patients were sensitive ex vivo to the induction chemotherapy and whether the extracts of (Anamu SC) and (P2Et) modulated the sensitivity of leukemic cells to death. Bone marrow samples were taken from 26 patients with de novo AL and 6 in relapse, and the cytotoxicity of the extracts alone or in combination with the chemotherapeutic was evaluated by XTT. Read More

Mol Ther Methods Clin Dev 2021 Mar 17;20:181-190. Epub 2020 Nov 17.

Department of Pediatric Onco-Immuno-Hematology, University Grenoble Alpes Hospital, Grenoble, France.

Intensive systemic chemotherapy is the gold standard of acute myeloid leukemia (AML) treatment and is associated with considerable off-target toxicities. Safer and targeted delivery systems are thus urgently needed. In this study, we evaluated a virus-like particle derived from the human type 3 adenovirus, called the adenoviral dodecahedron (Dd) to target AML cells. Read More

Nat Commun 2021 01 18;12(1):422. Epub 2021 Jan 18.

Centre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Université de Toulouse 3 Paul Sabatier, Equipe Labellisée LIGUE 2018, F-31037, Toulouse, France.

Drug tolerant/resistant leukemic stem cell (LSC) subpopulations may explain frequent relapses in acute myeloid leukemia (AML), suggesting that these relapse-initiating cells (RICs) persistent after chemotherapy represent bona fide targets to prevent drug resistance and relapse. We uncover that calcitonin receptor-like receptor (CALCRL) is expressed in RICs, and that the overexpression of CALCRL and/or of its ligand adrenomedullin (ADM), and not CGRP, correlates to adverse outcome in AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency, and sensitizes to cytarabine in patient-derived xenograft models. Read More

Transfus Med Hemother 2020 Dec 5;47(6):432-443. Epub 2020 Nov 5.

Department of Medicine III, University Hospital, Hematopoetic Cell Transplantation, Munich, Germany.

The prognosis of elderly patients with acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS) is limited due to the lack of therapy options and high relapse rates. Dendritic cell (DC)-based immunotherapy seems to be a promising treatment tool. DC are potent antigen-presenting cells and play a pivotal role on the interface of the innate and the adaptive immune system. Read More

Haematologica 2021 Jan 14. Epub 2021 Jan 14.

Catholic High-Performance Cell Therapy Center and Department of Medical Life Science, College of Medicine, The Catholic University, Seoul.

Chemoresistance of leukemic cells has largely been attributed to clonal evolution secondary to accumulating mutations. Here, we show that a subset of leukemic blasts in contact with the mesenchymal stroma undergo cellular conversion into a distinct cell type that exhibits a stem cell-like phenotype and chemoresistance. These stroma-induced changes occurred in a reversible and stochastic manner driven by cross-talk, whereby stromal contact induces IL-4 in leukemic cells that in turn targets the mesenchymal stroma to facilitate the development of new subset. Read More

Nat Commun 2021 01 11;12(1):241. Epub 2021 Jan 11.

Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

Acute myeloid leukemia (AML) is a typically lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, most AML retain wild-type TP53, encoding the pro-apoptotic tumor suppressor p53. MDM2 inhibitors (MDM2i), which activate wild-type p53, and BET inhibitors (BETi), targeting the BET-family co-activator BRD4, both show encouraging pre-clinical activity, but limited clinical activity as single agents. Read More

Am J Hematol 2021 03 28;96(3):379-394. Epub 2021 Jan 28.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include myelodysplastic syndromes with RS (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).

Diagnosis: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (MDS-RS-SLD/MLD), <5% bone marrow (BM) blasts, <1% peripheral blood blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). Read More

Int J Cancer 2021 Jun 18;148(11):2825-2838. Epub 2021 Jan 18.

Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.

To acquire a better understanding of clonal evolution of acute myeloid leukemia (AML) and to identify the clone(s) responsible for disease recurrence, we have comparatively studied leukemia-specific mutations by whole-exome-sequencing (WES) of both the leukemia and the nonleukemia compartments derived from the bone marrow of AML patients. The T-lymphocytes, B-lymphocytes and the functionally normal hematopoietic stem cells (HSC), that is, CD34 /CD38 /ALDH cells for AML with rare-ALDH blasts (<1.9% ALDH cells) were defined as the nonleukemia compartments. Read More