^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
CANCER:

Mast Cell Leukemia

2ms
Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis. (PubMed, Cancers (Basel))
The KITneg. SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816Vneg. patients.
Journal • Metastases
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT D816V • KIT D816H
3ms
Acute mast cell leukemia without KIT D816V mutation and lack of CD2 and CD25-a case report of rare entity. (PubMed, J Hematop)
The patient's severe symptoms were likely the result of organ damage from mast cell infiltration. Despite the use of intensive acute myeloid leukemia (AML)-like polychemotherapy, the patient died during the course of post-induction myelosuppression due to bleeding complications.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • TNFRSF8 (TNF Receptor Superfamily Member 8) • IL2RA (Interleukin 2 receptor, alpha) • CD2 (CD2 Molecule) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
|
KIT mutation • TNFRSF8 expression • KIT D816V
4ms
Review and Updates on Systemic Mastocytosis and Related Entities. (PubMed, Cancers (Basel))
Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.
Review • Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation
4ms
A Phase 1 Study of Avapritinib in Combination with Decitabine in Patients with Systemic Mastocytosis with an Associated Hematologic Neoplasm (ASH 2023)
Key exclusion criteria include a diagnosis of acute myeloid leukemia, history of intracranial hemorrhage or risk of major hemorrhage, prior treatment with avapritinib or decitabine with documented progression in SM or AHN component, respectively, or history of treatment with alternative KIT inhibitor or azacitidine within 4 weeks of study treatment initiation. Patients with platelet count ≥ 25 x 10 9/L and < 75 x 10 9/L, will receive lead-in dosing with decitabine or decitabine/cedazuridine with the ability to add avapritinib if sufficient platelet thresholds are achieved. This study will open at 7 sites in the United States and is anticipated to open in January 2024.
Clinical • P1 data • Combination therapy
|
SF3B1 (Splicing Factor 3b Subunit 1)
|
KIT mutation • SF3B1 mutation • KIT D816V
|
azacitidine • Ayvakit (avapritinib) • Inqovi (decitabine/cedazuridine)
4ms
Incidence and Prevalence of Mastocytosis in Adults: A Danish Nationwide Register Study (ASH 2023)
This nationwide register study provides updated data on the prevalence and incidence of mastocytosis in Denmark. The incidence rate was found to have an increasing trend until 2018 when it reached the highest value of 2,77 per 100. 000.
Clinical
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation
4ms
When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis. (PubMed, Genes (Basel))
NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.
Clinical • Observational data • Review • Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation
5ms
Safety and Efficacy of Bezuclastinib (CGT9486), a Novel, Highly Selective, Potent KIT D816V Tyrosine Kinase Inhibitor, in Patients with Advanced Systemic Mastocytosis (AdvSM): Results from Part 1 of the Phase 2 Apex Trial (ASH 2023)
Patients with a history of prior TKI therapy (e.g., avapritinib, midostaurin) are permitted in the trial. Enrollment in Part 1 of the Apex trial is complete. Patients enrolled in Part 1 of the Apex trial are generally representative of the population of patients with AdvSM based on patient characteristics and markers of disease. Part 1 includes a small subset of patients with prior use of TKIs.
Clinical • P2 data • Metastases
|
RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
KIT mutation • RUNX1 mutation • ASXL1 mutation • SRSF2 mutation • KIT D816V
|
Rydapt (midostaurin) • Ayvakit (avapritinib) • bezuclastinib (PLX9486)
5ms
Mast Cell Leukemia Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database (ASH 2023)
Conclusion This study presents updated clinicopathologic data from a large, pooled cohort of patients with MstCL. It identifies age, anemia, thrombocytopenia, leukemic presentation, complex cytogenetics, type of therapy, and quality of response to treatment as critical determinants of OS.
Clinical
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • TPSAB1 (Tryptase Alpha/Beta 1)
|
KIT mutation • KIT D816V
5ms
Antibody-Based and Cell Therapies for Advanced Mastocytosis: Established and Novel Concepts. (PubMed, Int J Mol Sci)
For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.
Review • Journal • Metastases
|
RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
KIT mutation • SRSF2 mutation • KIT D816V
5ms
Trial initiation date • Combination therapy • Metastases
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
|
azacitidine • elenestinib (BLU-263)
6ms
Profile of additional somatic mutations in KIT D816V positive advanced systemic mastocytosis (DGHO 2023)
A high KIT D816V VAF in PB and/or presence of HRM unveil a substantial proportion of pts with ‘masked’ SM-AMN. Clustering of HRM with other HRM frequently occurs and adversely impacts OS.
Metastases
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)
|
KIT mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • KIT D816V
6ms
Granularity in disease classification impacts survival prediction in advanced systemic mastocytosis: A single institution study of 329 informative cases. (PubMed, Am J Hematol)
Multivariable analysis that included the Mayo alliance risk factors for survival in SM (age >60 years, anemia, thrombocytopenia, increased alkaline phosphatase) revealed more accurate survival prediction with the ICC versus WHO classification order: (i) survival was significantly worse with MCL-immature versus MCL-mature (hazard ratio &lsqb;HR] 15; p < .01), (ii) prognostic distinction between MCL and SM-AHN/AMN was confirmed in the context of ICC (HR 9.3; p < .01) but not WHO classification order (p = .99), (iii) survival was similar between MCL-mature and SM-AMN (p = .18), and (iv) SM-AMN (HR 1.7; p < .01) but not SM-ALN (p = .37) was prognostically distinct from ASM. The current study provides evidence for the independent prognostic contribution of both the ICC system for SM-Adv and the Mayo alliance risk factors for survival in SM.
Journal • Metastases
6ms
Management of Advanced Systemic Mastocytosis and Associated Myeloid Neoplasms. (PubMed, Immunol Allergy Clin North Am)
A gain-of-function KIT D816 V mutation is the primary oncogenic driver found in about 90% of all patients with AdvSM. Midostaurin, an oral multikinase inhibitor with activity against KIT D816V, and avapritinib, an oral selective KIT D816V inhibitor are approved for AdvSM.
Review • Journal • Metastases
|
KIT mutation • KIT D816V
|
Rydapt (midostaurin) • Ayvakit (avapritinib)
7ms
Reappraisal of mast cell leukemia based on a single institution review of 16 cases: Mast cell morphology determines clinical outcome. (PubMed, Am J Hematol)
or well-differentiated displaying a round nucleus with condensed chromatin, and abundant dense cytoplasmic granulations. Immature mast cells include promastocytes and metachromatic blast-like forms.
Clinical data • Review • Journal
10ms
Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management. (PubMed, Am J Hematol)
Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM...Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era...Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.
Journal
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • IL2RA (Interleukin 2 receptor, alpha) • CD2 (CD2 Molecule)
|
NRAS mutation • KIT mutation • ASXL1 mutation • TNFRSF8 expression • SRSF2 mutation
|
imatinib • Rydapt (midostaurin) • cladribine • Ayvakit (avapritinib)
11ms
TRIAL IN PROGRESS: A PHASE II STUDY OF MIDOSTAURIN COMBINED WITH INDUCTION/CONSOLIDATION CHEMOTHERAPY AND AS SINGLE-AGENT MAINTENANCE IN PEDIATRIC PATENTS WITH FLT3-MUTATED ACUTE MYELOID LEUKEMIA (EHA 2023)
Midostaurin – an oral, multitargeted tyrosine kinase inhibitor – is approved in several countries, including Europe, where it is indicated for adult patients with newly diagnosed FLT3 mutation-positive ( FLT3+ ) AML in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response as single-agent during maintenance therapy. None, trial in progress. Acute myeloid leukemia, Clinical trial, Pediatric
Clinical • P2 data
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3 mutation
|
cytarabine • Rydapt (midostaurin) • daunorubicin
11ms
HUMAN CD117 AS AN IMMUNOTHERAPEUTIC TARGET IN PRECLINICAL MODELS OF ADVANCED SYSTEMIC MASTOCYTOSIS (EHA 2023)
Although the multi tyrosine kinase inhibitors (TKI) Midostaurin and Avapritinib are approved for the treatment of SM with overall response rates (ORR) of 75% for Avapritinib, the median overall survival ranges from 3.5 years (aggressive SM: ASM) to less than six months (mast cell leukemia: MCL). In conclusion, we demonstrate in preclinical SM models the efficient targeting and killing in vitro and in vivo by CAR T-cells directed against human CD117. Given that CD117 is expressed on healthy hematopoietic stem and progenitor cells (HSPCs) on a substantially lower level, there might be a therapeutic window for anti-CD117 immunotherapy in advanced forms ofmastocytosis. However, as CAR T-cells are highly efficient, collateral damage on healthy HSPCs will likely need to be compensated by subsequent HSC transplantation.
Preclinical • IO biomarker • Metastases
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • IL2 (Interleukin 2)
|
KIT mutation • KIT D816V
|
Rydapt (midostaurin) • Ayvakit (avapritinib)
12ms
Enrollment open • Combination therapy • Metastases
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
|
azacitidine • elenestinib (BLU-263)
12ms
Response and resistance to cladribine in patients with advanced systemic mastocytosis: a registry-based analysis. (PubMed, Ann Hematol)
In conclusion, cladribine is effective in 1L and 2L treatment of AdvSM. Mast cell leukemia, eosinophilia, application of < 3 cycles and a lack of response are adverse prognostic markers.
Journal • Metastases
|
RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
ASXL1 mutation • SRSF2 mutation
|
cladribine
12ms
AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)
P1/2, N=67, Not yet recruiting, Blueprint Medicines Corporation | N=108 --> 67 | Trial completion date: Nov 2027 --> Nov 2029 | Initiation date: Dec 2022 --> Apr 2023 | Trial primary completion date: Nov 2027 --> Nov 2029
Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy • Metastases
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion
|
azacitidine • elenestinib (BLU-263)
1year
Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. (PubMed, Proc Natl Acad Sci U S A)
Binding of SCF to this mutant fully restores the conformation of wild-type KIT dimers, including the formation of salt bridges responsible for D4 homotypic contacts and other hallmarks of SCF-induced KIT dimerization. These experiments reveal an unexpected structural plasticity of oncogenic KIT mutants and a therapeutic target in D5.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation • KIT wild-type
1year
Journal
|
CD4 (CD4 Molecule)
|
CD4 expression
1year
MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation. (PubMed, Int J Mol Sci)
MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD34 (CD34 molecule) • MIR1246 (MicroRNA 1246) • MITF (Melanocyte Inducing Transcription Factor) • MIR5100 (MicroRNA 5100)
|
KIT mutation • KIT expression
1year
Trial completion • Metastases
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT D816V
|
Ayvakit (avapritinib)
over1year
Capitalizing on paradoxical activation of the MAPK pathway for treatment of Imatinib-resistant mast cell leukemia. (PubMed, Hematol Oncol)
We observed that low concentrations of the TKIs Nilotinib and Ponatinib resulted in enhanced proliferation, suggesting paradoxical activation of the MAPK pathway...The combination of Ponatinib with the MEK inhibitor Trametinib, at nanomolar concentrations, effectively suppressed HMC-1.2 proliferation, metabolic activity, and induced apoptotic cell death...Effectiveness of this drug combination was recapitulated in the human KIT D816V MC line ROSA and in KIT D816V hematopoietic progenitors obtained from patient-derived induced pluripotent stem cells (iPS cells) and systemic mastocytosis patient samples. In conclusion, mutated KIT-driven Imatinib resistance and possible TKI-induced paradoxical activation can be efficiently overcome by a low concentration Ponatinib and Trametinib co-treatment, potentially reducing the negative side effects associated with MCL therapy.
Journal
|
BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT D816V • KIT V560G
|
Mekinist (trametinib) • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib)
over1year
Evolutionary Portrait of Adult Core-Binding Factor Leukemia Patients Treated with a Continuation Therapy with Midostaurin: Preliminary Results (ASH 2022)
Method Patients with de-novo CBFL received standard induction therapy with an anthracycline containing regimen ("7+3"-like) + Mido, three cycles of post-remission consolidation chemotherapy with high-dose cytarabine + Mido, and 12 months of Mido as Maintenance. Conclusion In patients with CBFL, we found FLT3 and/or KIT mutations actionable by a regimen consisting of intensive chemotherapy and Mido in 47% of cases. In two out of three relapsed cases the KIT mutation is maintained, although frequency of the mutant allele is lower at relapse, while all FLT3 and NRAS mutated patients lose the mutation upon disease relapse.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
|
NRAS mutation • FLT3-ITD mutation • FLT3 mutation • KIT mutation • KIT positive • CEBPA mutation
|
Oncomine Myeloid Assay GX
|
cytarabine • Rydapt (midostaurin)
over1year
Haploidentical Hematopoietic Cell Transplantation of Ex Vivo Tcrαβ-Depleted Grafts with CD45RA-Depleted Memory T Cell Add-Back Reduces Chronic Graft-Versus-Host Disease and Results in Favourable Gvhd-Relapse Free Survival: 5-Year Follow-up of 107 Patients Treated in a Multicenter Study in Singapore (ASH 2022)
All except 13 patients received the standard conditioning regimen of fludarabine 160mg/m2 divided daily over 4 days, thiotepa 10mg/kg divided twice daily for 1 day, and melphalan 70 – 140 mg/m2 for 1 day, in combination with either total lymphoid irradiation 6 Gy (n=58) or 7.5 Gy (n=12) over 3 equal fractions, total body irradiation of 2 Gy (n=24), or thymoglobuline (n=2). Short term GVHD prophylaxis was given for 30 days to 1 patient using MMF, 95 using tacrolimus, and 2 using sirolimus...10 patients with high donor-specific HLA antibodies (DSA) titres engrafted successfully after desensitisation with plasma exchange, rituximab, immunoglobulin, and irradiated donor buffy coat infusion (n=1)... Our preliminary results suggest that RIC haplo-HCT with TCRαβ and CD45RA+ depleted grafts allow successful allograft in patients with high-risk haematological malignancies lacking suitable matched donors, including patients with high levels of DSA. Acute GVHD was generally abortive, leading to low incidence of chronic GVHD and favorable GRFS. Best outcomes are seen in patients with favourable HCT-CI and low/intermediate risk DRI.
Preclinical
|
CD34 (CD34 molecule)
|
Rituxan (rituximab) • sirolimus • melphalan • fludarabine IV • thiotepa
over1year
The Use of Avapritinib in Advanced Systemic Mastocytosis: Report of an Open-Label Compassionate Use Program in the United Kingdom (ASH 2022)
Three patients were previously treated with other regimes - one patient with midostaurin, one with cladribine and one with azacytidine. This small cohort of patients reflects the clinical heterogeneity of AdvSM and mirrors the PATHFINDER trial outcomes in 'real world 'experience in the UK. Avapritinib as 1st line was tolerated, producing sustained clinical and pathological responses in the majority of this group of non-selected patients with AdvSM with high risk disease. Dose adjustments due to anticipated myelosuppression were made, with 72.2% of patients maintained on 100mg Avapritinib od.
Clinical
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
KIT mutation • SRSF2 mutation • KIT D816V
|
azacitidine • Rydapt (midostaurin) • cladribine • Ayvakit (avapritinib)
over1year
Mastocytosis and related entities: a practical roadmap. (PubMed, Acta Clin Belg)
There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics.Abbreviations: AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.
Journal • IO biomarker
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • TPSAB1 (Tryptase Alpha/Beta 1)
|
KIT mutation • KIT D816V
over1year
MPN-352 Clinicopathologic and Molecular Correlates of Organ Damage Across the Spectrum of Advanced Systemic Mastocytosis. (PubMed, Clin Lymphoma Myeloma Leuk)
In AdvSM, patterns of organ damage reflect disease subtype, prior therapy, and mutation profile. These data can help inform enrollment of AdvSM pts into clinical trials that currently require ≥1 organ damage findings. Grant Acknowledgments: ASH HONORS Award, NIH grant P30CA124435.
Observational data • Journal
|
RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
RUNX1 mutation • ASXL1 mutation • SRSF2 mutation • KIT D816V
|
Rydapt (midostaurin) • Ayvakit (avapritinib)
over1year
Clinicopathologic and Molecular Correlates of Organ Damage Across the Spectrum of Advanced Systemic Mastocytosis (SOHO 2022)
Patients or Other Participants: Our cohort included 240 AdvSM pts: 66 from the Stanford MPN registry and 174 from the phase I EXPLORER and phase II PATHFINDER studies of avapritinib in AdvSM...Compared to midostaurin-naïve pts, those who had received midostaurin had a greater bone marrow mast cell burden (P=0.06) but less frequently met WHO liver (P<0.001) and WHO malabsorption (P<0.001) criteria... In AdvSM, patterns of organ damage refl ect disease subtype, prior therapy, and mutation profi le. These data can help inform enrollment of AdvSM pts into clinical trials that currently require 1 organ damage fi ndings.
Clinical
|
RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
RUNX1 mutation • ASXL1 mutation • SRSF2 mutation • KIT D816V
|
Rydapt (midostaurin) • Ayvakit (avapritinib)
over1year
Journal
|
STK11 (Serine/threonine kinase 11)
|
STK11 mutation • KIT mutation • KIT D816H
over1year
Mast Cell Leukemia: Clinical and Molecular Features and Survival Outcomes of Patients in the ECNM Registry. (PubMed, Blood Adv)
In multivariate analysis (S/A/R mutations excluded due to low event rates), a diagnosis of MCL-AHN (HR 4.7, 95% CI 1.7 - 13.0, p = 0.001) and abnormal karyotype (HR 5.6, 95% CI 1.4 - 13.3, p = 0.02) were associated with inferior OS; KIT D816V positivity (HR 0.33, 95% CI 0.11 - 0.98, p = 0.04) and midostaurin treatment (HR 0.32, 95% CI 0.08 - 0.72, p = 0.008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
RUNX1 mutation • ASXL1 mutation • SRSF2 mutation • KIT D816V
|
Rydapt (midostaurin)
over1year
Mast cell leukemia with novel BRAF variant and concomitant atypical KIT variant. (PubMed, Cancer Genet)
This case provides evidence that MCL can have wide spectrum of genetic abnormalities as well as accumulation of mutations in various genes including BRAF. This finding may have significant implications for the understanding of pathogenesis, diagnosis, as well as targeted therapy of MCL.
Clinical • Review • Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF mutation • KIT exon 9 mutation
over1year
Systemic Mastocytosis and Other Entities Involving Mast Cells: A Practical Review and Update. (PubMed, Cancers (Basel))
We also summarize entities that require differential diagnosis, such as the recently reclassified SM subtype named bone marrow mastocytosis, mast cell leukemia (an SM subtype that can be acute or chronic); the rare morphological variant of all SM subtypes known as well-differentiated systemic mastocytosis; the extremely rare myelomastocytic leukemia and its differentiating features from mast cell leukemia; and mast cell activation syndrome. In addition, we provide a concise clinical update of the latest adjusted risk stratification model incorporating genomic data to define prognosis in SM and new treatments that were approved for advanced SM (midostaurin, avapritinib).
Review • Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation
|
Rydapt (midostaurin) • Ayvakit (avapritinib)
over1year
Mangifera Indica leaf extracts promote hair growth via activation of Wnt signaling pathway in human dermal papilla cells. (PubMed, Anim Cells Syst (Seoul))
Furthermore, hair growth was significantly enhanced in in vivo mice model treated with WEML. These results suggest that M. indica leave extract contains bioactive materials that can be used to treat hair loss.
Journal
|
DKK1 (dickkopf WNT signaling pathway inhibitor 1) • SRD5A2 (Steroid 5 Alpha-Reductase 2)
almost2years
Clinical Impact and Proposed Application of Molecular Markers, Genetic Variants and Cytogenetic Analysis in Mast Cell Neoplasms: Status 2022. (PubMed, J Allergy Clin Immunol)
Moreover, HαT more frequent in SM patients with Hymenoptera venom allergy and severe mediator-related symptoms than in SM patients without symptoms. Based on this knowledge, we propose a diagnostic algorithm in which genetic markers are applied together with clinical and histopathological criteria to establish the diagnosis and prognosis in SM.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
SRSF2 mutation • KIT D816V