News - PLCG2 mutation

11ms

Monoallelic expression can govern penetrance of inborn errors of immunity. (PubMed, Nature)

Allelic expression bias was also documented in phenotypically discordant family members with mutations in STAT1 and CARD11. This study highlights the importance of considering both the genotype and the 'transcriptotype' in analyses of the penetrance and expressivity of monogenic disorders.

11 months ago

Journal

JAK1 (Janus Kinase 1) • CARD11 (Caspase Recruitment Domain Family Member 11) • PLCG2 (Phospholipase C Gamma 2) • STAT1 (Signal Transducer And Activator Of Transcription 1)

PLCG2 mutation

1year

An unusual oral manifestation of chronic lymphocytic leukemia: A case report and review of the literature. (PubMed, J Am Dent Assoc)

Oral health care providers should include CLL in the differential diagnosis for multiple erythematous papules of the palatal mucosa, particularly in the presence of absolute lymphocytosis. Early recognition of oral manifestations associated with CLL can prompt a timely referral.

1 year ago

Review • Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • BTK (Bruton Tyrosine Kinase) • PAX5 (Paired Box 5) • PLCG2 (Phospholipase C Gamma 2)

PLCG2 mutation

Imbruvica (ibrutinib)

over1year

Mutational profile of previously treated chronic lymphocytic leukemia patients progressing on acalabrutinib or ibrutinib. (PubMed, Blood)

One acalabrutinib-treated patient and 4 ibrutinib-treated patients had emergent BTK/PLCG2 co-mutations. While common BTK C481 mutations were observed with both treatments, patterns of mutation and co-mutation frequency, mutation VAF, and uncommon BTK variants varied with acalabrutinib (T474I and E41V) and ibrutinib (L528W, A428D) in this patient population.

over 1 year ago

Journal

TP53 (Tumor protein P53) • PLCG2 (Phospholipase C Gamma 2)

TP53 mutation • BTK C481S • PLCG2 mutation • BTK mutation • BTK C481 • BTK T474I

Imbruvica (ibrutinib) • Calquence (acalabrutinib)

over1year

TRANSCEND-CLL-004: Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov)

P1/2, N=209, Recruiting, Juno Therapeutics, a Subsidiary of Celgene | Active, not recruiting --> Recruiting | Trial completion date: Jul 2026 --> Nov 2027 | Trial primary completion date: Jul 2026 --> Nov 2027

over 1 year ago

Enrollment open • Trial completion date • Trial primary completion date

PLCG2 (Phospholipase C Gamma 2) • CD5 (CD5 Molecule)

CD19 positive • PLCG2 mutation

Venclexta (venetoclax) • Imbruvica (ibrutinib) • Breyanzi (lisocabtagene maraleucel)

almost2years

AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma (clinicaltrials.gov)

P1, N=110, Recruiting, Carna Biosciences, Inc. | Phase classification: P1b --> P1

almost 2 years ago

Phase classification

PLCG2 (Phospholipase C Gamma 2)

PLCG2 mutation

docirbrutinib (AS-1763)

almost2years

Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL. (PubMed, Blood Adv)

Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment. NCT02251548.

almost 2 years ago

P2 data • Journal

TP53 (Tumor protein P53) • BTK (Bruton Tyrosine Kinase) • PLCG2 (Phospholipase C Gamma 2)

TP53 mutation • PLCG2 mutation • BTK mutation

Imbruvica (ibrutinib) • Rituxan (rituximab) • cyclophosphamide • fludarabine IV

almost2years

Overcoming Resistance in Chronic Lymphocytic Leukemia - Maybe Less is More? (PubMed, Clin Cancer Res)

Acquired mutations in BTK, PLCG2 and BCL2 are associated with resistance to continuous targeted agent therapy in chronic lymphocytic leukemia (CLL). Here, we discuss new evidence that limiting the duration of CLL therapy may prevent the evolution of such resistance mutations, potentially facilitating effective re-treatment strategies.

almost 2 years ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • BTK (Bruton Tyrosine Kinase) • PLCG2 (Phospholipase C Gamma 2)

PLCG2 mutation

2years

Curcumin Enhances Ibrutinib Induced Killing Effect Against TP53-Mutated Chronic Lymphocytic Leukemia Cells in Vitro (ASH 2023)

The results of Western blot showed that the protein expression levels of P65PI3K and p53 in the single drug group and the combination group were down-regulated in varying degrees, especially in the combination group（Figure 2). ConclusionIbrutinib combined with curcumin has synergistic killing effect on TP53- mutated CLL cells; Curcumin increases the killing effect of ibrutinib on TP53-mutated CLL cells by inhibiting PI3K and NFκB pathway, and degrading p53mt protein.

2 years ago

Preclinical • IO biomarker

TP53 (Tumor protein P53) • PLCG2 (Phospholipase C Gamma 2)

TP53 mutation • PLCG2 mutation • TP53 expression

Imbruvica (ibrutinib)

2years

Absence of BTK, BCL2, and PLCG2 Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax. (PubMed, Clin Cancer Res)

Of the 29 patients with PD, 19 have required retreatment (single-agent ibrutinib, n = 16, or ibrutinib plus venetoclax, n = 3); 17 achieved partial response or better, 1 achieved stable disease, and 1 is pending response assessment. First-line fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate development of resistance mechanisms associated with continuous single-agent targeted therapies, allowing for effective retreatment.

2 years ago

Journal • IO biomarker

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • BTK (Bruton Tyrosine Kinase) • IGH (Immunoglobulin Heavy Locus) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • PLCG2 (Phospholipase C Gamma 2) • POT1 (Protection of telomeres 1) • CHD2 (Chromodomain Helicase DNA Binding Protein 2)

TP53 mutation • BRAF mutation • ATM mutation • Chr del(11q) • EZH2 mutation • PLCG2 mutation • TS 12

Venclexta (venetoclax) • Imbruvica (ibrutinib)

2years

Molecular Analysis at Relapse of Patients Treated on the Ibrutinib and Rituximab Arm of the National Multi-Centre Phase III FLAIR Study in Previously Untreated CLL Patients (ASH 2023)

The majority of IR DP with BTK/PLCG2 mutations (6/8), were 100% homologous to germline IGHV unmutated, suggesting an inherent higher risk disease profile as a risk factor for acquiring BTKmt with prolonged BTKi therapy. BTK/PLCG2 mutations were enriched amongst very late progressors with 6/8 pts progressing shortly after stopping therapy at 72 mo., which is later than previously reported for relapsed/refractory CLL pts.

2 years ago

Clinical • P3 data

BRAF (B-raf proto-oncogene) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • BIRC3 (Baculoviral IAP repeat containing 3) • PLCG2 (Phospholipase C Gamma 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

BRAF mutation • ATM mutation • SF3B1 mutation • BTK C481S • PLCG2 mutation • BTK mutation • BTK C481R • BTK T474I

Imbruvica (ibrutinib) • Rituxan (rituximab)