Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.

The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche.

Fms -like tyrosine kinase 3 positive acute myeloid leukemia.

Purpose Of Review: Fms -like tyrosine kinase 3 (FLT3) mutations are common in newly diagnosed patients with acute myeloid leukemia (AML). They are associated with a high risk of relapse. The identification of FLT3 mutations has important implications for the management of AML.

Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis.

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow sclerosis, extra-medullary hematopoiesis, and possible transformation to acute leukemia. In the last decade, the molecular pathogenesis of the disease has been largely uncovered. Particularly, genetic and genomic studies have provided evidence of deregulated oncogenes in PMF as well as in other MPNs.

Treatment options for acute myeloid leukemia patients aged <60 years.

Treatment of acute myeloid leukemia (AML) has changed over the last few years, after the discovery of new drugs selectively targeting AML blasts. Although 3/7 remains the standard of care for most AML patients, several new targeted agents (such as FLT3 inhibitors, CPX-351, gemtuzumab ozogamicin, BCL-2 inhibitor, and oral azacitidine), either as single agents or combined with standard chemotherapy, are approaching clinical practice, starting a new era in AML management. Moreover, emerging evidence has demonstrated that high-risk AML patients might benefit from both allogeneic stem cell transplant and maintenance therapy, providing new opportunities, as well as new challenges, for treating clinicians.

Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial.

This phase 1b trial (NCT02670044) evaluated venetoclax-idasanutlin in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) ineligible for cytotoxic chemotherapy. Two-dimensional dose escalation (DE, n = 50) was performed for venetoclax daily with idasanutlin on days 1 to 5 in 28-day cycles, followed by dosing schedule optimization (n = 6) to evaluate reduced venetoclax schedules (21-/14-day dosing). Common adverse events (occurring in ≥40% of patients) included diarrhea (87.

Real-life efficacy and safety of idelalisib in 55 double-refractory follicular lymphoma patients.

Idelalisib, a reversible inhibitor of PI3Kδ (phosphoinositide-3 kinase delta), showed remarkable activity in the phase II DELTA trial, leading to its approval by the European Medicines Agency (EMA) in patients with relapsed/refractory (R/R) follicular lymphoma (FL). However, real-life data on idelalisib are scarce. We treated 55 double-refractory FL patients with idelalisib in a real-life setting.

Molecular Profiling of Kenyan Acute Myeloid Leukemia Patients.

Acute myeloid leukemia (AML) is an infrequent disease, and it is associated with high morbidity and mortality. It harbors a unique configuration of cytogenetic abnormalities and molecular mutations that can be detected using microscopic and molecular methods respectively. These genetic tests are core elements of diagnosis and prognostication in high-income countries.

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death.

Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma.

Altered cellular energetic metabolism has recently emerged as important feature of neoplastic cells. Indeed, interfering with cancer cell metabolism might represent a suitable therapeutic strategy. In this study, we aimed to assess glucose metabolism activation in human lymphomas and evaluate how metformin can exert its action on lymphoma cells.

Immunological Response Against SARS-COV-2 After BNT162b2 Vaccine Administration Is Impaired in Allogeneic but Not in Autologous Stem Cell Transplant Recipients.

The efficacy of Covid-19 vaccine in hematopoietic stem cell transplantation (HSCT) recipients is still unknown. We planned a prospective study to evaluate the immune response after the administration of Covid-19 vaccine in HSCT recipients. Fifty patients previously submitted to HSCT (38 autologous and 12 allogeneic) received the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech).

COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies.

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis.

Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib.

Tyrosine kinase inhibitors (TKIs) have radically changed the outcome of chronic myeloid leukemia (CML) patients in the last 20 years. Moreover, the advent of second generation TKIs, namely nilotinib and dasatinib, have largely increased the number of CML patients achieving deep and sustained molecular responses. However, the possible mechanisms capable of influencing the maintenance of the long-term molecular response are not yet fully known and understood.

Immunotherapy in Acute Myeloid Leukemia: Where We Stand.

In the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interest. A better understanding of immunological escape and systemic tolerance induced by AML blasts has been achieved.

Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia.

Background: Hairy-cell leukemia (HCL) is a CD20+ indolent B-cell cancer in which a BRAF V600E kinase-activating mutation plays a pathogenetic role. In clinical trials involving patients with refractory or relapsed HCL, the targeting of BRAF V600E with the oral BRAF inhibitor vemurafenib led to a response in 91% of the patients; 35% of the patients had a complete response. However, the median relapse-free survival was only 9 months after treatment was stopped.

Iron Toxicity and Chelation Therapy in Hematopoietic Stem Cell Transplant.

Many patients with hematologic malignancies receive RBC transfusion support, which often causes systemic and tissue iron toxicity. Because of their compromised bone marrow function, hematopoietic stem cell transplant (HSCT) recipients are especially vulnerable to excess iron levels. Iron toxicity may compromise transplant engraftment and eventually promote relapse by mediating oxidative and genotoxic stress in hematopoietic stem cells (HSCs) and further impairing the already dysfunctional bone marrow microenvironment in HSCT recipients.

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study.

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19.

Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19.

The Yin and Yang of the Bone Marrow Microenvironment: Pros and Cons of Mesenchymal Stromal Cells in Acute Myeloid Leukemia.

Mesenchymal stromal cells (MSCs) have, for a long time, been recognized as pivotal contributors in the set up and maintenance of the hematopoietic stem cell (HSC) niche, as well as in the development and differentiation of the lympho-hematopoietic system. MSCs also have a unique immunomodulatory capacity, which makes them able to affect, both and , the function of immune cells. These features, namely the facilitation of stem cell engraftment and the inhibition of lymphocyte responses, have both proven essential for successful allogeneic stem cell transplantation (allo-SCT), which remains the only curative option for several hematologic malignancies.

Chemotherapy-Induced Tumor Cell Death at the Crossroads Between Immunogenicity and Immunotolerance: Focus on Acute Myeloid Leukemia.

In solid tumors and hematological malignancies, including acute myeloid leukemia, some chemotherapeutic agents, such as anthracyclines, have proven to activate an immune response via dendritic cell-based cross-priming of anti-tumor T lymphocytes. This process, known as immunogenic cell death, is characterized by a variety of tumor cell modifications, i.e.

BCR-ABL Independent Mechanisms of Resistance in Chronic Myeloid Leukemia.

Not all chronic myeloid leukemia (CML) patients are cured with tyrosine kinase inhibitors (TKIs), and a proportion of them develop resistance. Recently, continuous BCR-ABL gene expression has been found in resistant cells with undetectable BCR-ABL protein expression, indicating that resistance may occur through kinase independent mechanisms, mainly due to the persistence of leukemia stem cells (LSCs). LSCs reside in the bone marrow niche in a quiescent state, and are characterized by a high heterogeneity in genetic, epigenetic, and transcriptional mechanisms.