The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients.

The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours.

Targeting Apoptosis in AML: Where Do We Stand?

More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival.

Alterations in microRNA Expression during Hematopoietic Stem Cell Mobilization.

microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation.

The role of NF-κB and Smac/DIABLO proteins in the treatment response and survival of acute myeloid leukemia patients.

Introduction: The misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).

Material And Methods: The aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.

Results: Expression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively.

Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG).

We present the results of a prospective, non-randomized phase 2 trial in which 253 AML patients (pts) under 60 years old received DAC (Daunorubicin + AraC + Cladribine) as first induction followed by CLAM (Cladribine + AraC + Mitoxantrone) as early second induction on day 16 based on bone marrow (BM) blasts on day 14 (D14). The CR/CRi rate after a single course of DAC was 83% for pts with D14 BM blasts less than 10%. Forty-six pts had >10% BM blasts on D14, of whom 35 received CLAM with rates of CR/CRi 60% and early death (ED) 23%.

The efficacy of sapacitabine in treating patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) remains a poor prognosis hematological malignancy. The introduction of aggressive chemotherapy with allogeneic stem cell transplantation has resulted in improved clinical outcomes in younger patients. However, the treatment results in unfit elderly AML population remain disappointing.

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial.

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients.

Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia.

The inhibitor of apoptosis protein (IAP) family acts as an inhibitor of apoptosis pathways. The potential prognostic value of the expression of selected IAP family members, XIAP, cIAP-1, cIAP-2 and survivin protein, was evaluated with regard to treatment response and survival of 56 newly diagnosed adult patients with acute myeloid leukemia (AML). The presence of these IAP members influenced the achievement of a complete response (CR).

Angiopoietins in haematopoietic stem cell mobilisation in patients with haematological malignancies.

Background: The bone marrow niche contains different types of cells including osteoblasts and endothelial progenitors, all of which interact and take part in the process of mobilisation. The aim of our study was to evaluate the levels of cytokines (osteopontin and angiopoietins 1 and 2) active in the bone marrow niche during the mobilisation of haematopoietic stem cells for autologous transplantation.

Materials And Methods: Forty-eight patients (24 females, 24 males), median age 56.

The kinetics of hematopoietic niche cytokines and their influence on mobilization efficacy and timing in patients with hematological malignancies.

The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM-1, VEGF, MMP-9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years.

Jagged-1: a new promising factor associated with favorable prognosis in patients with acute myeloid leukemia.

In this study Jagged-1 and Dll-1 surface expression as well as Notch-1 receptor intracellular domain (Notch-1-IC) expression were assessed by multi-color flow cytometry in leukemic blasts obtained from 88 patients with acute myeloid leukemia (AML). CD34+peripheral blood stem cells (PBSCs) were used as a control. The median expression of Jagged-1 and Dll-1 was significantly higher in AML blasts than in PBSCs (p=0.

Polymorphism of CD44 influences the efficacy of CD34(+) cells mobilization in patients with hematological malignancies.

In the last decade, peripheral blood was the main source of hematopoietic stem cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms of HSC mobilization are still not clear and the efficacy of the procedure is hardly predictable. Ligand-receptor interactions of adhesion molecules, such as SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of HSC in the hematopoietic niche.

Circulating endothelial cell kinetics and their potential predictive value during mobilization procedure.

Objective: Circulating endothelial cells (CECs) in patients with hematological malignancies are assessed as a noninvasive marker of angiogenesis. The aim of this study was to evaluate the numbers of CECs and their subsets during mobilization of hematopoietic stem cells.

Patients And Methods: Thirty-eight patients were enrolled to the study (19 females and 19 males) at median age of 56.

The kinetics and apoptotic profile of circulating endothelial cells in autologous hematopoietic stem cell transplantation in patients with lymphoproliferative disorders.

In neoplastic disorders, endothelial cells take part in tumor progression and also influence the recovery of hematopoiesis after high-dose chemotherapy. Measurements of circulating endothelial cells (CEC), their subsets and kinetics were taken in patients with lymphoid malignancies (37 multiple myeloma, ten lymphoma) during autologous hematopoietic stem cell transplantation (HSCT). CEC were evaluated by four-color flow cytometry at different time points.

Influence of high expression of Smac/DIABLO protein on the clinical outcome in acute myeloid leukemia patients.

The role of the Smac/DIABLO protein, a novel apoptosis agonist, in acute myeloid leukemia (AML) is not clearly determined. The expression of Smac/DIABLO protein in AML leukemic cells and its relationship with clinical outcome was evaluated in this study. The intracellular expression of Smac/DIABLO protein was assessed using multi-color flow cytometry in 71 newly diagnosed AML patients treated with conventional chemotherapy.