An updated outlook on autophagy mechanism and how it supports acute myeloid leukemia maintenance.

The gradual acquisition of genetic and epigenetic disturbances bestows malignant traits upon hematopoietic stem cells, subverting them into a founder and reservoir cell for de novo acute myeloid leukemia (AML) known as leukemic stem cells (LSC). Beyond its molecular heterogeneity, AML is also characterized by rewiring biological processes to support its onset and maintenance. LSC were observed to inherently and actively trigger mitochondrial turnover through selective autophagic removal such that impairing the process led to cell differentiation at the expense of its stemness.

Early death and intracranial hemorrhage prediction in acute promyelocytic leukemia: validation of a risk score in a chemotherapy plus ATRA cohort from an international consortium.

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External validation and calibration of the HoLISTIC Consortium's advanced-stage Hodgkin lymphoma international prognostic index (A-HIPI) in the Brazilian Hodgkin lymphoma registry.

The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A-HIPI model, developed in 2022 for advanced-stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5-year follow-up.

Microcosting analysis of haematopoietic stem cell transplantation and chemotherapy with intermediate doses of cytarabine in the treatment of acute myeloid leukaemia.

Background: Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and effectiveness do not differ between consolidation therapy with intermediate-dose cytarabine or auto-HSCT, and so the cost can help physicians and health managers in their choice.

NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma.

Multiple myeloma (MM) is a prevalent hematological malignancy with high recurrence and no definitive cure. The current study revisits the role of the IGF1/IGF1R axis in MM, introducing a novel inhibitor, NT157. The IGF1/IGF1R pathway is pivotal in MM, influencing cell survival, proliferation, and migration and impacting patient survival outcomes.

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3R-driven cells.

Myeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2 increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2 positive cells.

Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.

TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed.

Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

Background: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration).

Case Presentation: A 40-year-old woman was submitted to a second kidney transplant.

NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells.

Combination therapies or multi-targeted drugs have been pointed out as an option to prevent the emergence of resistant clones, which could make long-term treatment more effective and translate into better clinical outcomes for cancer patients. The NT157 compound is a synthetic tyrphostin that leads to long-term inhibition of IGF1R/IRS1-2-, STAT3- and AXL-mediated signaling pathways. Given the importance of these signaling pathways for the development and progression of lung cancer, this disease becomes an interesting model for generating preclinical evidence on the cellular and molecular mechanisms underlying the antineoplastic activity of NT157.

Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel.

Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists.

Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazilian specialists.

Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2 driven cells.

Myeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have reported cytotoxic effects in cellular and murine models of MPN, but no consensus has been reached regarding the potency and efficacy of inhibitors of the IGF1R-related pathway in this context.

Phenformin increases early hematopoietic progenitors in the Jak2 murine model.

Background: Myeloproliferative neoplasms (MPN) are disorders characterized by an alteration at the hematopoietic stem cell (HSC) level, where the JAK2 mutation is the most common genetic alteration found in classic MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis). We and others previously demonstrated that metformin reduced splenomegaly and platelets counts in peripheral blood in JAK2 pre-clinical MPN models, which highlighted the antineoplastic potential of biguanides for MPN treatment. Phenformin is a biguanide that has been used to treat diabetes, but was withdrawn due to its potential to cause lactic acidosis in patients.

STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells.

Stathmin 1 (STMN1) is a microtubule-destabilizing protein highly expressed in hematological malignancies and involved in proliferation and differentiation. Although a previous study found that the PML-RARα fusion protein, which contributes to the pathophysiology of acute promyelocytic leukemia (APL), positively regulates STMN1 at the transcription and protein activity levels, little is known about the role of STMN1 in APL. In this study, we aimed to investigate the STMN1 expression levels and their associations with laboratory, clinical, and genomic data in APL patients.

Comprehensive analysis of cytoskeleton regulatory genes identifies ezrin as a prognostic marker and molecular target in acute myeloid leukemia.

Purpose: Despite great advances that have been made in the understanding of the molecular complexity of acute myeloid leukemia (AML), very little has been translated into new therapies. Here, we set out to investigate the impact of cytoskeleton regulatory genes on clinical outcomes and their potential as therapeutic targets in AML.

Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas (TCGA) AML study and used for survival and functional genomics analyses.

MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model.

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.

New germline GATA1 variant in females with anemia and thrombocytopenia.

Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We investigated the genetic scenario and possible patterns of transmission in a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters, age 41 and 42, revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase.