Treatment-Free Remission in Chronic Phase Chronic Myeloid Leukemia After Nilotinib De-Escalation: 96-Week Update of the DANTE Study.

Treatment-free remission (TFR) in chronic myeloid leukemia (CML) can be considered for patients in sustained deep molecular response (DMR) who can discontinue tyrosine kinase inhibitors (TKIs) while maintaining responses. Studies suggest that TKI de-escalation before TFR is feasible. This phase II study evaluated nilotinib de-escalation outcomes in adults with CML in chronic phase (CP) treated with first-line nilotinib for ≥ 3 years and in sustained DMR for ≥ 1 year.

Neutrophil-to-Lymphocyte ratio as surrogate for JAK2 suppression and event-free survival in polycythemia vera.

Chronic systemic inflammation is a key driver of polycythemia vera (PV) progression, but the immunomodulatory effects of current treatments remain poorly defined. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker of systemic inflammation proven in other contexts, but its role in monitoring PV disease activity has not been established. Using data from three of the largest PV clinical trials, we evaluated the effects of PV therapies on NLR and its relationship with molecular response and clinical outcomes.

Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm with a substantial risk of thromboembolic events (TEs), which contribute to morbidity and mortality. Traditional thrombotic risk stratification primarily considers age and thrombosis history, yet these parameters alone do not capture the complexity of thrombotic risk. Growing evidence highlights the role of additional factors influencing the risk of TEs, underscoring the need for a more comprehensive approach to patient stratification.

Real-World Efficacy Profile of Compassionate Use of Asciminib in an Italian, Multi-Resistant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patient Population.

Chronic myeloid leukemia (CML) patients who have experienced failure and/or intolerance to multiple lines of treatment have limited therapeutic possibilities. Asciminib is a first-in-class tyrosine kinase inhibitor (TKI) that inhibits the ABL Myristoyl Pocket (STAMP or Specifically Targeting the ABL Myristoyl Pocket) within the BCR::ABL1 oncoprotein. This retrospective Italian analysis reports the efficacy and safety outcomes of asciminib in treating 77 CML patients in chronic phase (CML-CP) within a compassionate use setting.

SETD2 loss of function is a recurrent event in advanced-phase chronic myeloid leukemia and contributes to genomic instability: SETD2 loss in Chronic Myeloid Leukemia.

The SETD2 tumour suppressor encodes a histone methyltransferase that specifically trimethylates histone H3 on lysine 36 (H3K36me3), a key histone mark implicated in the maintenance of genomic integrity among other functions. We found that SETD2 protein deficiency, mirrored by H3K36me3 deficiency, is a nearly universal event in advanced-phase chronic myeloid leukemia (CML) patients. Similarly, K562 and KCL22 cell lines exhibited markedly reduced or undetectable SETD2/H3K36me3 levels, respectively.

Bone Marrow CD34+/lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) After 12 Months of Nilotinib Treatment Exhibit a Different Gene Expression Signature Compared to the Diagnosis and the Corresponding Cells from Healthy Subjects.

Background: Chronic-Phase Chronic Myeloid Leukemia (C-PCML) is defined by the presence of the fusion gene, which encodes a tyrosine kinase protein that drives the uncontrolled proliferation and survival of leukemic stem cells (LSCs). Nilotinib, a tyrosine kinase inhibitor, targets the activity of BCR-ABL1 by reducing aberrant signaling pathways, which drive the regeneration of LSCs. Despite nilotinib's action, a population of resilient LSCs persist in the bone marrow (BM) and can indeed drive relapse and progression in CML patients.

Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis.

Introduction: In patients with myelofibrosis (MF), overall survival (OS) after ruxolitinib discontinuation is poor, with leukemic transformation, clonal evolution and thrombocytopenia as the main factors worsening prognosis.

Patients And Methods: To assess the impact of disease phenotype on outcome after ruxolitinib discontinuation in chronic phase patients, we performed a sub-analysis of the "RUX-MF" study (NCT06516406), which now includes 1055 MF patients who received ruxolitinib in a real-life context.

Results: After a median follow-up of 3.

-mutated myeloproliferative neoplasms.

Calreticulin (CALR) is a chaperone protein that plays a crucial role in protein folding quality control and calcium homeostasis. Mutations in result in a mutated protein lacking key calcium-binding sites and the KDEL sequence, leading to a constitutive activation of the MPL-JAK2-STAT5 pathway, which is involved in the pathogenesis of essential thrombocythemia (ET) and primary myelofibrosis (PMF). Despite advancements in understanding the role of mutations, current therapeutic strategies remain focused on managing symptoms and complications, with allogeneic stem cell transplantation (alloHSCT) as the only curative option.

Digital PCR (dPCR) is able to anticipate the achievement of stable deep molecular response in adult chronic myeloid leukemia patients: results of the DEMONSTRATE study.

Chronic Myeloid Leukemia (CML) is marked by the BCR::ABL1 fusion gene. Monitoring tyrosine kinase inhibitor (TKI) therapy response is crucial for treatment management, thus, limitations in Reverse Transcription quantitative PCR's (RT-qPCR) accuracy and sensitivity led to the exploration of alternative methods like digital PCR (dPCR). This study evaluated dPCR efficacy in detecting Minimal Residual Disease (MRD) in CML patients undergoing TKI therapy.

Prognostic and Predictive Models in Myelofibrosis.

Purpose Of Review: Myelofibrosis (MF) includes prefibrotic primary MF (pre-PMF), overt-PMF and secondary MF (SMF). Median overall survival (OS) of pre-PMF, overt-PMF and SMF patients is around 14 years, seven and nine years, respectively. Main causes of mortality are non-clonal progression and transformation into blast phase.

Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis.

Despite increased understanding of the genomic landscape of Myeloproliferative Neoplasms (MPNs), the pathological mechanisms underlying abnormal megakaryocyte (Mk)-stromal crosstalk and fibrotic progression in MPNs remain unclear. We conducted mass spectrometry-based proteomics on mice with Romiplostim-dependent myelofibrosis to reveal alterations in signaling pathways and protein changes in Mks, platelets, and bone marrow (BM) cells. The chemokine Platelet Factor 4 (PF4)/Cxcl4 was up-regulated in all proteomes and increased in plasma and BM fluids of fibrotic mice.

Red cell distribution width and prognosis in myelofibrosis patients treated with ruxolitinib.

We evaluated RDW in a single-center series of 61 consecutive patients with primary and secondary MF at diagnosis and during treatment with ruxolitinib (RUX) and examined any possible prognostic impact. Elevated RDW values were present in all but 4 patients at diagnosis with a median RDW of 18.9%.