Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia.

Purpose: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE.

Patients And Methods: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day).

Adaptation to glucose starvation is associated with molecular reorganization of the circadian clock in .

The circadian clock governs rhythmic cellular functions by driving the expression of a substantial fraction of the genome and thereby significantly contributes to the adaptation to changing environmental conditions. Using the circadian model organism we show that molecular timekeeping is robust even under severe limitation of carbon sources, however, stoichiometry, phosphorylation and subcellular distribution of the key clock components display drastic alterations. Protein kinase A, protein phosphatase 2 A and glycogen synthase kinase are involved in the molecular reorganization of the clock.

Many People With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary.

What Is This Summary About?: This is a plain language summary of a publication describing long-term results from the RESONATE-2 study with up to 8 years of follow-up. The original paper was published in in June 2022.

What Were The Results?: Researchers looked at 269 adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had not received any treatment for their CLL/SLL.

Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia.

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.

Characterization of low-grade arthralgia, myalgia, and musculoskeletal pain with ibrutinib therapy: pooled analysis of clinical trials in patients with chronic lymphocytic leukemia and mantle cell lymphoma.

Joint and muscle pain, including arthralgia, myalgia, and musculoskeletal pain, are among the common adverse events (AEs) reported for ibrutinib, a once-daily Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). This pooled analysis from nine clinical trials of ibrutinib in CLL and MCL ( = 1178) evaluated patterns of these AEs. Any grade arthralgia, myalgia, and musculoskeletal pain occurred in 18%, 10%, and 6% of patients, respectively.

Expression of the translation termination factor eRF1 is autoregulated by translational readthrough and 3'UTR intron-mediated NMD in Neurospora crassa.

Eukaryotic release factor 1 (eRF1) is a translation termination factor that binds to the ribosome at stop codons. The expression of eRF1 is strictly controlled, since its concentration defines termination efficiency and frequency of translational readthrough. Here, we show that eRF1 expression in Neurospora crassa is controlled by an autoregulatory circuit that depends on the specific 3'UTR structure of erf1 mRNA.

Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial.

Importance: Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia is a poor prognostic feature and limits use of Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor ruxolitinib.

Objective: To compare the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia.

Quantitative assessment of JAK2 V617F and CALR mutations in Philadelphia negative myeloproliferative neoplasms.

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation.

Patients And Methods: Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis.

The small G protein RAS2 is involved in the metabolic compensation of the circadian clock in the circadian model .

Accumulating evidence from both experimental and clinical investigations indicates a tight interaction between metabolism and circadian timekeeping; however, knowledge of the underlying mechanism is still incomplete. Metabolic compensation allows circadian oscillators to run with a constant speed at different substrate levels and, therefore, is a substantial criterion of a robust rhythm in a changing environment. Because previous data have suggested a central role of RAS2-mediated signaling in the adaptation of yeast to different nutritional environments, we examined the involvement of RAS2 in the metabolic regulation of the clock in the circadian model organism We show that, in a -deficient strain, the period is longer than in the control.

Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary.

Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification.

Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial.

Background: Available therapies for myelofibrosis can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia. Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited myelosuppression in phase 1/2 trials. We aimed to assess the efficacy and safety of pacritinib versus best available therapy in patients with myelofibrosis irrespective of baseline cytopenias.

[Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia].

Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy.

Stroke in essential thrombocythemia.

Background: Our aim was to assess the incidence and the special characteristics of stroke, as a severe complication of patients diagnosed with essential thrombocythemia (ET).

Methods: A retrospective analysis was carried out on 102 patients with ET enrolled and analyzed from the period between 1999 and 2012. Patients with one or more strokes were selected.