Abstract 3409: MSK-IMPACT Heme: Validation and clinical experience of a comprehensive molecular profiling platform for hematologic malignancies

Ptashkin, Ryan; Benayed, Ryma; Ziegler, John B.; Rema, Anoop Balakrishnan; Sadowska, Justyna; Kiecka, Iwona; Ho, Caleb; Yao, Jinjuan; Moung, Christine; Petrova‐Drus, Kseniya; Nafa, Khédoudja; Batlevi, Connie Lee; Tallman, Martin S.; Levine, Ross L.; Giralt, Sergío; Younes, Anas; Ladanyi, Marc; Berger, Mike; Zehir, Ahmet; Arcila, Maria E.

doi:10.1158/1538-7445.sabcs18-3409

Cited by 4 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address adequacy issues, between 10–40 sections (5 µm thick) were used for extraction. Samples were sequenced using the MSK‐IMPACT HEME assay, a hybridization capture‐based next‐generation sequencing panel capturing all coding regions of 400 genes, 16 and the MSK‐Pan Heme Fusion assay, an RNA‐based gene fusion detection assay which utilizes the ArcherDx Anchored Multiplex polymerase chain reaction (PCR) (AMP™) technology and targets 199 genes. Matched normal control DNA from all 9 patients (4 FFPE non‐neoplastic tissue, 3 nail clippings, 2 blood samples) was used for paired tumor: normal analysis to ensure only somatic variant calling.…”

Section: Methodsmentioning

confidence: 99%

Next generation sequencing of breast implant‐associated anaplastic large cell lymphomas reveals a novel STAT3‐JAK2 fusion among other activating genetic alterations within the JAK‐STAT pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

Breast implant associated anaplastic large cell lymphoma (BIA‐ALCL) is a distinct type of ALCL, and a new provisional entity by the 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. In contrast to systemic and primary cutaneous ALCLs, BIA‐ALCLs have been genetically characterized by the absence of fusions and frequent activation of the JAK‐STAT3 pathway through mutations in JAK1 and STAT3. In this study, we report the results of the genetic profiling of 9 BIA‐ALCL cases supporting the role of the JAK‐STAT pathway activation in this entity, including the identification of an activating STAT3‐JAK2 fusion similar to those recently reported in T‐cell lymphoproliferative disorders of the gastrointestinal tract. To our knowledge, this is the first fusion reported in BIA‐ALCL, providing further insight into the overall genetic landscape of this rare entity as well as uncovering potential options for targeted therapy in cases with advanced disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Next generation sequencing of breast implant‐associated anaplastic large cell lymphomas reveals a novel STAT3‐JAK2 fusion among other activating genetic alterations within the JAK‐STAT pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…If both were available, data from BMA were used preferentially (for details see Supplemental Methods). 15,16…”

Section: Cytogenetic and Molecular Datamentioning

confidence: 99%

Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia

et al. 2022

View full text Add to dashboard Cite

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre‐treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre‐treatment next‐generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo‐SCT). Induction chemotherapy led to MRD− remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD‐. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD− remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD− remission. Patients with fewer individual clones were more likely to achieve MRD− remission. Among 132 patients who underwent allo‐SCT, outcomes were favorable whether patients achieved early MRD− after induction or later MRD− after subsequent therapy prior to allo‐SCT. As MRD conversion with chemotherapy prior to allo‐SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.

show abstract

Implications of TP53 Allelic State for Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

Bernard

Nannya

Devlin

et al. 2019

Preprint

View full text Add to dashboard Cite

TP53 mutations are associated with poor clinical outcomes and treatment resistance in myelodysplastic syndromes. However, the biological and clinical relevance of the underlying mono-or bi-allelic state of the mutations is unclear. We analyzed 3,324 MDS patients for TP53 mutations and allelic imbalances of the TP53 locus and found that 1 in 3 TP53 -mutated patients had mono-allelic targeting of the gene whereas 2 in 3 had multiple hits consistent with bi-allelic targeting. The established associations for TP53 with complex karyotype, high-risk presentation, poor survival and rapid leukemic transformation were specific to patients with multi-hit state only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System, while mono-allelic patients did not differ from TP53 wild-type patients. The separation by allelic state was retained in therapy-related MDS. Findings were validated in a cohort of 1,120 patients. Ascertainment of TP53 allelic state is critical for diagnosis, risk estimation and prognostication precision in MDS, and future correlative studies of treatment response should consider TP53 allelic state.

show abstract

Abstract 3409: MSK-IMPACT Heme: Validation and clinical experience of a comprehensive molecular profiling platform for hematologic malignancies

Cited by 4 publications

References 0 publications

Next generation sequencing of breast implant‐associated anaplastic large cell lymphomas reveals a novel STAT3‐JAK2 fusion among other activating genetic alterations within the JAK‐STAT pathway

Next generation sequencing of breast implant‐associated anaplastic large cell lymphomas reveals a novel STAT3‐JAK2 fusion among other activating genetic alterations within the JAK‐STAT pathway

Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia

Implications of TP53 Allelic State for Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

Contact Info

Product

Resources

About