Targeted next generation sequencing of <scp>PDGFRB</scp> rearranged myeloid neoplasms with monocytosis

Patnaik, Mrinal M.; Lasho, Terra L.; Finke, Christy; Pardanani, Animesh; Tefferi, Ayalew

doi:10.1002/ajh.24267

Cited by 21 publications

(19 citation statements)

References 7 publications

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“…While a previous study of three PDGFRB rearranged case 11 did not show any mutation, we identified mutated cases. Both discrepancies could be the consequence of small cohort sizes and a heterogeneous disease group.…”

Section: Fgfr1contrasting

confidence: 59%

Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2

et al. 2018

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Section: Fgfr1contrasting

confidence: 59%

Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2

et al. 2018

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“…Chromosomal translocations involving PDGFRA/B have been associated with myeloid neoplasms characterized by prominent eosinophilia and responsiveness to imatinib . At times, PDGFR rearranged myeloid neoplasms can present with monocytosis and BM dysplasia, but given their unique responsiveness to imatinib, these are no longer classified as CMML . Patients presenting with a clinical phenotype of CMML with eosinophilia, should be assessed for t(5;12)(q31‐q32;p13), giving rise to the ETV6(TEL)‐PDGFRB fusion oncogene .…”

Section: Diagnosismentioning

confidence: 99%

“…At times, PDGFR rearranged myeloid neoplasms can present with monocytosis and BM dysplasia, but given their unique responsiveness to imatinib, these are no longer classified as CMML . Patients presenting with a clinical phenotype of CMML with eosinophilia, should be assessed for t(5;12)(q31‐q32;p13), giving rise to the ETV6(TEL)‐PDGFRB fusion oncogene . The association between monocytosis and PDGFRA rearrangements is uncommon .…”

Section: Diagnosismentioning

confidence: 99%

Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

2019

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Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 10 9 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in~30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 10 9 /L, hemoglobin <10 g/dL, platelet count <100 × 10 9 /L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively.Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of~40%-50% and complete remission rates of~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.

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“…Chromosomal translocations involving PDGFRA/B have been associated with myeloid neoplasms characterized by prominent eosinophilia and responsiveness to imatinib . At times, PDGFR rearranged myeloid neoplasms can present with monocytosis and BM dysplasia, but given their unique responsiveness to imatinib, these are no longer classified as CMML . Patients presenting with a clinical phenotype of CMML with eosinophilia, should be assessed for the t(5;12)(q31–q32;p13), giving rise to the ETV6(TEL)‐PDGFRB fusion oncogene .…”

Section: Diagnosismentioning

confidence: 99%

Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management

Patnaik

Tefferi

2016

American J Hematol

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 × 109/L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20–30% of patients, while >90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML‐specific prognostic models include; the Groupe Français des Myélodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age >65 years, WBC >15 × 109/L, anemia, platelets <100 × 109/L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count >10 × 109/L, hemoglobin <10 g/dL, platelets <100 × 109/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (≥3 risk factors), intermediate‐2 (2 risk factors), intermediate‐1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively. Hypomethylating agents such as 5‐azacitidine and decitabine are commonly used, with overall response rates of ∼30–40% and complete remission rates of ∼7–17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. Am. J. Hematol. 91:632–642, 2016. © 2016 Wiley Periodicals, Inc.

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Targeted next generation sequencing of PDGFRB rearranged myeloid neoplasms with monocytosis

Cited by 21 publications

References 7 publications

Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2

Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2

Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management

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