Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Eldfors, Samuli; Kuusanmäki, Heikki; Kontro, Mika; Majumder, Muntasir Mamun; Parsons, Alun; Edgren, Henrik; Pemovska, Tea; Kallioniemi, Olli; Wennerberg, Krister; Gökbuget, Nicola; Burmeister, Thomas; Porkka, Kimmo; Heckman, Caroline A.

doi:10.1016/s0959-8049(16)61481-8

Cited by 2 publications

(2 citation statements)

References 19 publications

(21 reference statements)

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“…30 was implemented for calling somatic mutations, and mutation annotations were performed using SnpEff 4.04 31 as described previously. 32 Gene copy number variants (CNVs) were identified using the CopyCat tool (https://github.com/chrisamiller/copycat). Cytogenetics data were generated using fluorescence in situ hybridisation technology as described previously, 33 following European Myeloma Network 2012 guidelines.…”

Section: Sample Collection and Plasma Cell Enrichmentmentioning

confidence: 99%

Prognostic significance of esterase gene expression in multiple myeloma

et al. 2021

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Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

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Section: Sample Collection and Plasma Cell Enrichmentmentioning

confidence: 99%

Prognostic significance of esterase gene expression in multiple myeloma

et al. 2021

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“…For filtering of germline variants, we used genomic DNA extracted from a matched skin biopsy acquired at TP3. The experimental and analytic pipeline has previously been described 43 . In short, genomic DNA was amplified and sequencing libraries were produced by exome capture of 3 μg DNA and the NimbleGen SeqCap EZ v2 capture kit (Roche NimbleGen, Madison, WI, USA).…”

Section: Methodsmentioning

confidence: 99%

Converging molecular evolution in acute myeloid leukaemia

Engen

Hellesøy

Dowling

et al. 2020

Preprint

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Acute myeloid leukaemia (AML) is a highly heterogeneous disease. Here, we decipher the disease composition of a single AML patient through longitudinal sampling scrutinized by high-resolution genetic and phenotypic approaches, including sequencing, immunophenotyping, ex vivo drug sensitivity testing and establishment of patient-derived xenograft models. Throughout the disease course we identified patterns of both divergent and convergent molecular evolution within the leukemic compartment. We identified at least six discrete leukaemia initiating cell populations, of which five were characterised by known recurrent mutations in AML. These populations partly correlated with immunophenotypically defined cell subsets, drug sensitivity profiles and population-specific potential for engraftment in immunodeficient mice. Our results indicate that the genetic and phenotypic development are closely intertwined, and that diversity in the leukaemic gene-environment likely influences disease trajectories.

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Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Cited by 2 publications

References 19 publications

Prognostic significance of esterase gene expression in multiple myeloma

Prognostic significance of esterase gene expression in multiple myeloma

Converging molecular evolution in acute myeloid leukaemia

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