News - CALR mutation - LARVOL VERI

Lysosomal Degradation Targets Mutant Calreticulin and the Thrombopoietin Receptor in Myeloproliferative Neoplasms. (PubMed, Blood Adv)

mTOR inhibition also reduces colony formation and differentiation of CD34+ cells from MPN patients but not healthy donors. Together, these findings indicate low surface MPL as a biomarker of mutant CRT-mediated MPN and induced degradation of CRTDel52 and MPL as an avenue for therapeutic intervention.

4 days ago

Journal

CD34 (CD34 molecule) • CALR (Calreticulin) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

CALR mutation

13d

Chronic myeloproliferative neoplasms with concomitant CALR mutation and BCR::ABL1 translocation: diagnostic and therapeutic implications of a rare hybrid disease. (PubMed, Front Cell Dev Biol)

The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.

13 days ago

Review • Journal

ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

29d

Activating mutations in JAK2 and CALR differentially affect intracellular calcium flux in store operated calcium entry. (PubMed, Cell Commun Signal)

This report highlights the impact of JAK2 and CALR mutations on Ca2+ flux (store depletion and SOCE) in response to stimulation with EPO and TPO. The study shows that the JAK2-V617F mutation strongly alters the regulatory mechanism of EpoR/JAK2-dependent intracellular calcium balance, affecting baseline calcium levels, EPO-induced calcium entry, and PLCγ-1 signaling pathways. Our results reveal an important role of calcium flux in the homeostasis of JAK2-V617F positive cells.

29 days ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

JAK2 V617F • JAK2 mutation • CALR mutation

Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm (clinicaltrials.gov)

P1, N=10, Recruiting, Marina Kremyanskaya | Trial completion date: Jan 2025 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026

1 month ago

Trial completion date • Trial primary completion date

CALR (Calreticulin)

CALR mutation

Hiltonol (poly-ICLC)

2ms

Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients. (PubMed, Turk J Haematol)

JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

2 months ago

Retrospective data • Journal

CALR (Calreticulin)

JAK2 V617F • CALR mutation

hydroxyurea

2ms

Comparison of Clinical Characteristics of JAK2, CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations. Among ET patients, JAK2 mutation is most common. Compared with CALR group, the thrombotic rate, WBC and Fg significantly increase in JAK2 group, while PLT decrease. Compared with triple-negative group, the incidence of splenomegaly and HCT significantly increase. Compared with CALR group, Fg significantly increases but APTT decreases in triple-negative group.

2 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

2ms

CALR-mutated patients with low allele burden represent a specific subtype of essential thrombocythemia: A study on behalf of FIM and GBMHM. (PubMed, Am J Hematol)

A low allele burden (i.e., <20%) of the CALR driver mutation is found in 10.8% of CALR-mutated MPNs, mostly in essential thrombocythemia, and correlates with a milder phenotype and a more indolent evolution compared to patients with an allele burden ≥20%.

2 months ago

Journal

CALR (Calreticulin)

CALR mutation

2ms

Detecting Multiple Driver Mutations in a Patient with Essential Thrombocythemia. (PubMed, Am J Case Rep)

She was started on aspirin alone as she was less than 60 years old and had no history of thrombotic events...CONCLUSIONS We propose that in patients with a low JAK2 V617 allele variant, testing for other driver mutations should be performed. In our patient, JAK2 mutation could be clonal hematopoiesis of indeterminate potential; therefore, the dominant mutation (CALR) would determine the disease phenotype.

2 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • JAK2 mutation • CALR mutation

aspirin

3ms

Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination. (PubMed, Front Oncol)

Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of BCR::ABL1 and JAK2 co-occurrence. The interaction between JAK2 and BCR::ABL1 clones during the disease course as well as therapy and outcome are presented.

3 months ago

Review • Journal

ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

3ms

Type 1 CALR mutation allele frequency correlates with CD34/CXCR4 expression in myelofibrosis-type megakaryocyte dysplasia: A mechanism of disease progression? (PubMed, Blood Cancer J)

No abstract available

3 months ago

Journal

CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD34 (CD34 molecule) • CALR (Calreticulin)

CALR mutation • CXCR4 expression

3ms

Abdominal venous thromboses: detection of the JAK2 p.V617F mutation by next-generation ultradeep sequencing-A prevalence study of patients in Mecklenburg-West Pomerania (2017-2021). (PubMed, Front Med (Lausanne))

By analyzing peripheral blood for the mutation JAK2 p.V617F, an important cause of these rare thrombotic events can be identified. The development of a diagnostic workup with next-generation ultradeep sequencing for the analysis of the JAK2 p.V617F mutation and further mutations has the potential to better understand the etiology of abdominal venous thromboses in individual patients in regional clinical care, as abdominal venous thromboses are diagnosed by various medical disciplines.

3 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin) • MPL (MPL Proto-Oncogene, Thrombopoietin Receptor)

JAK2 V617F • JAK2 mutation • CALR mutation

3ms

One thousand patients with essential thrombocythemia: the Mayo Clinic experience. (PubMed, Blood Cancer J)

Aspirin therapy appeared to mitigate both arterial (HR 0.4) and venous (HR 0.4) thrombosis risk. HR-based risk models delineated patients with median survivals ranging from 10 years to not reached and 20-year leukemia/myelofibrosis incidences from 3%/21% to 12.8%/49%. The current study provides both novel and confirmatory observations of essential thrombocythemia.

3 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

3ms

One thousand patients with essential thrombocythemia: the Florence-CRIMM experience. (PubMed, Blood Cancer J)

Cytoreductive therapy appeared to mitigate both venous (HR 0.3; p = 0.01) and arterial thrombosis (HR 4; p = 0.04); there was a trend for aspirin in preventing arterial thrombosis recurrence. The current study provides real-world observations in essential thrombocythemia, representing a valid source document for interpreting current literature and planning future studies.

3 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

3ms

CALR mutation burden in essential thrombocythemia and disease outcome. (PubMed, Blood)

Among 281 patients with essential thrombocythemia and calreticulin mutation, we found a variant allele frequency of >60% to be associated with significantly shortened myelofibrosis-free survival, mostly apparent with CALR type-1 and CALR type-indeterminate mutations.

3 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • CALR (Calreticulin)

CALR mutation

3ms

A germline JAK2 exon12 mutation and a late somatic CALR mutation in a patient with essential thrombocythemia. (PubMed, Front Oncol)

We further demonstrated that JAK2N533S, as a noncanonical JAK2 exon12 mutation, is a germline mutation that may not exert an effect on cell proliferation and protein function. These results and the present body of available data imply that certain noncanonical JAK2 mutations are not gain-of-function mutations leading to the development of myeloproliferative neoplasms.

3 months ago

Journal

JAK2 (Janus kinase 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

4ms

JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms. (PubMed, Colomb Med (Cali))

Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

4 months ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • CALR mutation

4ms

Ruxolitinib Phosphate and Chemotherapy Given Before and After Reduced Intensity Donor Stem Cell Transplant in Treating Patients With Myelofibrosis (clinicaltrials.gov)

P1, N=18, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

4 months ago

Trial completion

JAK2 (Janus kinase 2) • CALR (Calreticulin)

CALR mutation

Jakafi (ruxolitinib) • sirolimus • melphalan • fludarabine IV

4ms

Correlation between IPSET-t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience. (PubMed, Ann Hematol)

We found no correlation between hemorrhagic risk and gender or mutational status. Results of our study highlight the validity of IPSET-t score in predicting individual hemorrhagic risk among ET patients, suggesting a possible role of IPSET-t scoring system as a global evaluator for vascular events in ET patients.

4 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

5ms

Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT. (PubMed, Bone Marrow Transplant)

Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%...Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

5 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

busulfan

5ms

Clonal hematopoiesis and its evolution of myeloproliferative neoplasms (PubMed, Zhonghua Yi Xue Za Zhi)

Although great progress has been made in the understanding of MPN clonal hematopoiesis and its evolution with the development of next-generation sequencing, there are still many limitations. In this study, we mainly discuss gene mutations of MPN and their influences on the thrombosis, leukemia and fibrosis transformation, and the influencing factors of clonal evolution, aiming to summarize the influence of clonal hematopoiesis and its evolution on the complications, prognosis and survival of MPN.

5 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • JAK2 mutation • CALR mutation

5ms

Clinical Study of Lymphocyte Subsets in Patients with BCR/ABL Negative Myeloproliferative Neoplasms (ASH 2023)

Among 123 patients with MPN,57 patients were diagnosed with ET with a median age of 62 years (range, 20-86), 17 patients were diagnosed with PV with a median age of 53 years (range, 19-70), 49 patients were diagnosed with PMF with a median age of 63 years (range, 26-81). 55 patients had varying degrees of splenomegaly, of which 14 (24. 6%) patients with ET, 32 (65.

5 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CALR (Calreticulin)

JAK2 V617F • CALR mutation

5ms

Real-World Experience of Ropeginterferon-Alfa Treatment of PV and ET - Two Centers Experience (ASH 2023)

Prior to ropeginterferon-alfa, the participants were managed with therapeutic phlebotomies, or cytoreduced with either hydroxyurea, pegylated interferon-alpha 2a ( Pegasys), JAK2 inhibitors, or were newly diagnosed and previously untreated. Ropeginterferon-alfa is effective in PV and ET, however, the dose that achieves CHR is highly individualized, necessitating an incremental titration approach. The patients already in CHR from prior therapy needed relatively lower doses of ropeginterferon-alfa to maintain CHR. Clinical trials are ongoing with an alternate accelerated dosing scheme and results are awaited.

5 months ago

Clinical • Real-world evidence • Real-world

DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CALR (Calreticulin)

DNMT3A mutation • TET2 mutation • CBL mutation • JAK2 V617F • JAK2 mutation • CALR mutation

Pegasys (pegylated interferon α -2a) • hydroxyurea

5ms

Risk Factors for Thrombosis in Essential Thrombocythemia: A Clinico-Pathological Study of 138 Patents in a Middle Eastern Population (ASH 2023)

Our ET patient population had high prevalence of MPL (Pro106Leu) mutation which may be germ line in nature as previously reported, and correspondingly lowered the prevalence of JAK2V617F and CALR mutations in our cohort. Thrombosis developed in 26. 8% patients.

5 months ago

Clinical

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • JAK2 mutation • CALR mutation

5ms

Exploratory Study on Impact of Comorbid Sleep Apnea Treatment in Patients with Polycythemia Vera and Essential Thrombocythemia (ASH 2023)

Given the significant likelihood of OSA in patients with PV and ET (as based on STOP-BANG scores of 3 or more), there is need to evaluate and treat for OSA. Preliminary results show abnormalities in inflammatory markers with reductions in C-reactive protein and erythropoietin levels following CPAP therapy even though mixed results were noted in inflammatory and HIF-target gene transcripts, and markers of iron turnover. Larger studies and longer follow-up are required to understand the impact of OSA on not only the thrombotic and inflammatory milieu in patients with MPNs, but also the benefit of treating on prevention of disease progression and thrombotic manifestations common in MPNs.

5 months ago

Clinical

IL6 (Interleukin 6) • CALR (Calreticulin) • CRP (C-reactive protein) • SLC2A1 (Solute Carrier Family 2 Member 1)

JAK2 V617F • CALR mutation • VEGFA expression

5ms

Combined Myeloid and Lymphoid Malignancies in 13 Elderly Patients (ASH 2023)

The limitations of this study are its small size, single community investigator, retrospective clinical nature, and the lack of gene sequencing and other molecular studies in most if not all of the patients. This observation was noted over three years in a single community practice which strongly implies that combined occurrence may be more common than recognized and suggests that further investigation is warranted.

5 months ago

Clinical

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • JAK2 mutation • CALR mutation

5ms

Red Cells Distribution Width and Prognosis in Myelofibrosis Patients Treated with Ruxolitinib (ASH 2023)

ConclusionsRed cells distribution width may represent a good integrative measure of several disease processes and also has prognostic significance at the time of MF diagnosis and during RUX treatment. Even though our preliminary observations are limited by the small number of patients and need to be further confirmed by larger studies, we can speculate that RDW may help in the rapid detection of MF patients with a poor prognosis, which can only partially be improved from currently available targeted therapies with JAK inhibitors.

5 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • TGFB1 (Transforming Growth Factor Beta 1) • CALR (Calreticulin)

JAK2 V617F • CALR mutation

Jakafi (ruxolitinib)

5ms

Utility of Assessing Primary Hemostasis By Determining Platelet Function and Von Willebrand Factor in Patients with Myeloproliferative Neoplasms (ASH 2023)

Von Willebrand antigen (VWF: Ag) (normal: 60-160 U/dL), von Willebrand factor (VWF) activity (VWF: GPIbM) (normal: 60-160 U/dL) and closure time with the platelet function analyzer (PFA-200) (pathological: collagen-Epinephrine channel > 200 seconds; collagen-ADP channel > 140 seconds) were assessed...ASA resistance was associated with a higher platelet count and higher VWF: GPIbM. 50% of the patients with increased VWF: GPIbM (>160 U/dL) had resistance to ASA, showing VWF: GPIbM as an independent variable in the multivariate analysis.

5 months ago

Clinical • Tumor mutational burden

TMB (Tumor Mutational Burden) • JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

5ms

Calr+ Myelofibrosis/BCR-ABL Chronic Myeloid Leukemia Overlap Syndrome Treated with Asciminib (ASH 2023)

Treatment was ruxolitinib and hydroxyurea...He started dasatinib and decitabine, which resulted in a drop from 28...However, hyperuricemia and renal failure led to a change in regimen and the patient was started on asciminib and ropeginterferon alfa-2b-njft in January 2022...He received cladribine and cytarabine, but was found to have leukemic infiltration of the spinal cord five months later...However, he always maintained a high CALR burden. This patient's mutational profile and disease course argue for the importance of early testing for CALR and BCR-ABL in addition to JAK2 and MPL in the setting of an MPN and for further research into the underlying causes of these overlap conditions.

5 months ago

Tumor mutational burden

TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • CALR (Calreticulin)

ASXL1 mutation • NRAS G12 • CALR mutation • NRAS G12V

dasatinib • cytarabine • Jakafi (ruxolitinib) • decitabine • Scemblix (asciminib) • cladribine • hydroxyurea • Besremi (ropeginterferon alfa-2b)

5ms

A Real World, Single-Centre Study of Young Adult Patients with Philadelphia Negative Myeloproliferative Neoplasms (ASH 2023)

5%; 25/55) and hydroxycarbamide (43...8%) receiving warfarin rather than a DOAC...Whilst traditionally younger patients are considered to have ‘low risk’ disease, this real-world study highlights a significant thrombosis rate of ~ 20% which may have associated morbidity considering the relatively longer duration of the disease course and need for cytoreductive therapy. Specific AYA MPN directed risk stratification and therapeutic algorithms are required to inform holistic and age-appropriate patient management.

5 months ago

Clinical • Real-world evidence • Real-world

NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CALR (Calreticulin)

JAK2 V617F • CALR mutation

hydroxyurea

5ms

Young patients with myelofibrosis have distinct clinicomolecular features, favorable prognosis, and commonly exhibit inflammatory comorbidities. (PubMed, Ann Hematol)

MF is rare in young adults, has distinct clinical/molecular correlates, and a favorable prognosis. The high frequency of inflammatory comorbidities and their correlation with progression of disease risk clinically highlights the role of inflammation in MF pathogenesis.

5 months ago

Journal

CALR (Calreticulin)

CALR mutation

5ms

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis. (PubMed, Nat Commun)

We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.

5 months ago

P2 data • Journal

CALR (Calreticulin)

JAK2 V617F • CALR mutation

tamoxifen

5ms

Molecular diagnostic criteria of myeloproliferative neoplasms. (PubMed, Expert Rev Mol Diagn)

The genomic landscape of the MPN has evolved in the last 15 years with integration of next-generation sequencing becoming the gold standard of MPN management. Although diagnostics and prognostication have become more personalized, additional studies are required to translate these molecular findings into targeted therapy therefore improving patient outcomes.

5 months ago

Review • Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

CALR mutation

5ms

FEDRATINIB MAY BE THE FIRST CHOICE FOR PATIENTS AFFECTED BY MYELOFIBROSIS AND CONCURRENT LYMPHOPROLIFERATIVE DISORDER OR DEVELOPED AFTER ANOTHER JAK INHIBITOR THERAPY (SIE 2023)

The first-in-class JAK inhibitor ruxolitinib (RUX) can control the disease, splenomegaly, and systemic symptoms. The data presented in this report allows us to suggest FED in the first line for patients harboring indolent lymphoid clones, closely monitoring potential progressions, and as a second line JAKi in case of the development of LPD during RUX therapy. Understanding the underlying biological processes could help treat these patients at best in the future.

5 months ago

Clinical

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

Jakafi (ruxolitinib) • Inrebic (fedratinib)

5ms

CLINICAL AND BIOLOGICAL RELEVANCE OF JAK2V617F VARIANT ALLELE FREQUENCY ≤2% IN A MONOCENTRIC SERIES OF CASES OF SUSPECTED MYELOPROLIFERATIVE NEOPLASMS (SIE 2023)

Therefore in patients with JAK2V617F VAF ≤1% clinical, histopathological and genetic data must be integrated for a proper assessment. Patients with JAK2V617F VAF ≤1% and no overt MPN should be monitored to evaluate possible development of hematological malignancies and/or complications such as thrombotic events and solid tumors.

5 months ago

Clinical

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • CALR mutation

6ms

The telomerase inhibitor imetelstat differentially targets JAK2V617F versus CALR mutant myeloproliferative neoplasm cells and inhibits JAK-STAT signaling. (PubMed, Front Oncol)

Hence, our data demonstrate that imetelstat reduces TL and targets JAK/STAT signaling, particularly in CALR-mutated cells. Although the exact patient subpopulation who will benefit most from imetelstat needs to be defined, our data propose that CALR-mutated clones are highly vulnerable.

6 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • JAK2 (Janus kinase 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD34 (CD34 molecule) • CALR (Calreticulin) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

KRAS mutation • JAK2 V617F • STAT3 expression • CALR mutation

imetelstat (GRN163L)

6ms

Germline MPL mutations may be a rare cause of "triple-negative" thrombocytosis. (PubMed, Exp Hematol)

Although clear evidence concerning treatment of HT is still lacking, individuals with HT should probably not be given a cytoreductive treatment. Thus, a correct diagnosis is pivotal to avoid unnecessary treatments.

6 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 mutation • CALR mutation

6ms

Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis. (PubMed, Nat Commun)

Third, homozygous CALR mutations result in high endoplasmic reticulum (ER) stress, responding to ER stressors and unfolded protein response inhibition. Overall, our integrated analyses provide a molecularly motivated roadmap for individualized myelofibrosis patient treatment.

6 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

CALR mutation

6ms

Impact of Clinical and Genetic Factors on Myelofibrosis Outcomes after Allogeneic Transplantation (ASH 2023)

Of note, ruxolitinib was available for use post-2011 only, following its FDA approval that year...Majority (77.1%) had HLA-matched donors, underwent reduced intensity (69.3%) HCT with peripheral blood stem-cells (92.2%) and received tacrolimus/methotrexate based GVHD prophylaxis (90.1%)... In this single-institution retrospective analysis, the presence of a JAK2-V617F mutation was associated with better OS and PFS following HCT in MF in the post-2011 era. Survival outcomes are significantly better in the post-2011 era compared to pre-2011, in our cohort.

6 months ago

Clinical

TP53 (Tumor protein P53) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)

TP53 mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • U2AF1 mutation • JAK2 V617F • JAK2 mutation • CALR mutation

Jakafi (ruxolitinib) • methotrexate

6ms

Prognostic Significance and Clinical Correlations of Myeloid Mutations in Myelofibrosis Based on Their Functional Class (ASH 2023)

Current analysis revealed distinctive clinical characteristics and survival outcomes associated with specific categories of mutated myeloid genes in pts with PMF, largely overlapping with the ICC defined "myelodysplasia-related gene mutations" category.

6 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • CALR (Calreticulin) • SH2B3 (SH2B Adaptor Protein 3) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • SRSF2 mutation • U2AF1 mutation • NFE2L2 mutation • CALR mutation