When basic science reaches into rational therapeutic design: from historical to novel leads for the treatment of β-globinopathies
Purpose of review
β-hemoglobinopathies, such as β-Thalassemias (β-Thal) and sickle cell disease (SCD) are among the most common inherited genetic disorders in humans worldwide. These disorders are characterized by a quantitative (β-Thal) or qualitative (SCD) defects in adult hemoglobin production, leading to anemia, ineffective erythropoiesis and severe secondary complications. Reactivation of the fetal globin genes (γ-globin), making-up fetal hemoglobin (HbF), which are normally silenced in adults, represents a major strategy to ameliorate anemia and disease severity.
Recent findings
Following the identification...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Small molecule therapeutics to treat the β-globinopathies
Purpose of review
The current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies.
Recent findings
Recent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies.
Summary
We summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target for therapeutic pu...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Distinguishing atypical chronic myeloid leukemia from other Philadelphia-negative chronic myeloproliferative neoplasms
Purpose of review
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative, is a rare myelodysplastic/myeloproliferative neoplasm (MDS/MPN) characterized by leukocytosis, granulocytic dysplasia, and typically poor patient outcomes. Since its first description as a variant CML lacking the Philadelphia chromosome (Ph), the diagnostic criteria for aCML have evolved significantly. Nevertheless, distinguishing it from other Ph-negative myeloid neoplasms can still be very challenging, and given its generally worse prognosis, this is a clinically important distinction. The purpose of this review is to conceptualize our under...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Recent advances in allogeneic hematopoietic cell transplantation for acute myeloid leukemia
Purpose of review
Allogeneic hematopoietic cell transplantation (HCT), with associated graft-versus-leukemia effects, remains the best postremission strategy for patients with intermediate or high-risk acute myeloid leukemia (AML), with a curative potential. Here, we highlight recent advances in allogeneic HCT that broadened access, refined prognostication, and improved outcomes of AML patients undergoing this procedure.
Recent findings
Eligibility for allogeneic HCT continued to expand to AML patients older than 60 years, as well as to patients lacking human leukocyte antigen (HLA)-matched donors with the advent of a...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Relapsed or primary refractory AML: moving past MEC and FLAG-ida
Purpose of review
Treatment of relapsed and refractory acute myeloid leukemia (AML) is still very challenging, with poor response rates and low chance for cure. This is especially true when treating patients who are elderly, have multiple comorbidities, or who are too unfit for traditional salvage chemotherapy regimens.
Recent findings
Recently, advances in the treatment of relapsed/refractory AML utilizing novel chemotherapy combinations, hypomethylating, and targeted therapies have shown promising results.
Summary
Several early-phase studies with novel targeted therapy combinations have demonstrated encouraging r...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment
Purpose of review
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes. It typically manifests as asymptomatic skin lesions and cytopenias, which result from bone marrow involvement. Less commonly, it will present in lymph nodes or visceral organs as well. Although rare, BPDCN has been discussed more frequently in recent years as new drugs have been developed that could be effective at treating this disease.
Recent findings
Until recently, treatment for BPDCN commonly included intensive chemotherapy regimens, which are generally reserved f...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Optimal therapeutic strategies for mixed phenotype acute leukemia
Purpose of review
Mixed phenotype acute leukemia (MPAL) encompasses a rare group of clinically, immunophenotypically, and genetically diverse leukemias. Diagnosing and treating these patients remains challenging. In recent years, systematic efforts have been made to better define the genetic landscape of MPAL. These insights allow better understanding of the pathophysiology of MPAL, have the potential for a more biologically meaningful classification and may promote targeted, novel approaches to treat these leukemias.
Recent findings
Recent studies suggest that MPALs originate in a multipotent primitive cell, demonstr...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Myeloid sarcoma
Purpose of review
Myeloid sarcoma; also known as granulocytic sarcoma and chloroma, often occurs concomitantly with AML, and rarely without bone marrow involvement. In this article, we review the recent literature on myeloid sarcoma, focusing on treatment approach for this rare disease, and addressing the prognostic and therapeutic role of molecular and cytogenetic aberrations.
Recent findings
Molecular testing and cytogenetics are important adjunct to conventional diagnostic methods. The significance of cytogenetic and molecular abnormalities in myeloid sarcoma is not completely established, but testing for targetabl...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Detection and management of acute myeloid leukemia measurable residual disease: is it standard of care?
Purpose of review
In the present manuscript, we will review the current approaches to investigate measurable residual disease (MRD) and its clinical applications in AML management.
Recent findings
Over the last decades, several methods have been developed to trace MRD, with flow cytometry and polymerase chain reaction (PCR) being the most reliable. However, new technologies, such as digital PCR and Next-Generation Sequencing are emerging as particularly useful in AML. The 2017 European LeukemiaNet (ELN) recommendations have incorporated MRD assessment to define the response criteria to therapy, and more recently, the ...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Hypomethylating agents with venetoclax: have we discovered the holy grail?
Purpose of review
Since its approval in November 2018, venetoclax with a hypomethylating agent backbone has shown promising efficacy for older, newly diagnosed acute myeloid leukemia (AML) patients who are unfit for standard intensive induction chemotherapy. This regimen is well tolerated, allows for deep and durable responses and may be increasing the prevalence of the disease. Although there is justifiable excitement, it remains to be seen to what extent venetoclax-based regimens, as they are currently administered, will have a long-term impact on the treatment of AML. This review aims to evaluate the strengths of the ...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Tumor protein 53 mutations in acute myeloid leukemia: conventional induction chemotherapy or novel therapeutics
Purpose of review
Tumor protein 53 (TP53) protein is involved in fundamental processes of cancer, aging, and DNA repair. Thus, TP53 dysfunction is implicated in malignant processes and remains the most commonly mutated gene in cancer but represents a relatively small proportion in acute myeloid leukemia (AML). Patients with TP53-mutated AML attain inferior responses to therapy resulting in poor overall outcomes.
Recent findings
Traditional treatment approaches with conventional chemotherapy yields suboptimal responses for patients with TP53 mutant AML compared with wildtype TP53. In recent years, there is increasing i...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Novel therapies in myelodysplastic syndromes
Purpose of review
Currently, there is a rapid expansion of novel, efficacious therapies for the treatment of patients with myelodysplastic syndromes (MDS) at a rate never seen to date. In this review, we will outline new treatment strategies in MDS focusing on novel hypomethylating agents (HMA) and combinations in addition to targeted and immune-based therapies.
Recent findings
Large-scale gene sequencing and immune-based research has given us a great deal of information regarding the complexity and heterogeneity of MDS. This rapid improvement in our knowledge has provided a framework for development of novel therapie...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Driver mutations in acute myeloid leukemia
Purpose of review
The mutational landscape of acute myeloid leukemia (AML) has revised diagnostic, prognostic, and therapeutic schemata over the past decade. Recurrently mutated AML genes have functional consequences beyond typical oncogene-driven growth and loss of tumor suppresser function.
Recent findings
Large-scale genomic sequencing efforts have mapped the complexity of AML and trials of mutation-based targeted therapy has led to several FDA-approved drugs for mutant-specific AML. However, many recurrent mutations have been identified across a spectrum from clonal hematopoiesis to myelodysplasia to overt AML, su...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research
