Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor   gene

Walz, Christoph; Metzgeroth, Georgia; Haferlach, Claudia; Schmitt‐Graeff, Annette; Fabarius, Alice; Hagen, Volker; Prümmer, Otto; Rauh, Stefan; Hehlmann, Rüdiger; Hochhaus, Andreas; Cross, Nicholas C. P.; Reiter, Andreas

doi:10.3324/haematol.10980

Cited by 86 publications

(68 citation statements)

References 44 publications

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“…In contrast, conventional cytogenetics analysis generally permits identification of cases of BMM associated with a PDGFRB rearrangement (i.e., chromosomal translocations involving 5q31-32) [18]. These cases with PDGFRA/PDGFRB-rearranged MPN with BM MC hyperplasia are appropriately classified as "Myeloid or lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1" per the WHO classification [10].…”

Section: Molecular Studiesmentioning

confidence: 99%

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Pardanani

2015

American J Hematol

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Disease overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.Risk stratification: The 2008 World Health Organization classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent SM (ISM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.Management: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (+/−corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases.Investigational Drugs: Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 90:251–262, 2015. © 2015 Wiley Periodicals, Inc.

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Section: Molecular Studiesmentioning

confidence: 99%

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Pardanani

2015

American J Hematol

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“…Since then, a large variety of fusion partners for PDGFRB have been described, most of which, however, are single case reports (Table 4). [23][24][25][26][27][28][29][30][31][32][33][34][35][36] Despite the rare frequency (o1%) of PDGFRB rearrangements in cytogenetically defined cases of chronic myelomonocytic leukemia and other myeloid neoplasms (for example, atypical CML, juvenile myelomonocytic leukemia, chronic basophilic leukemia, myelodysplastic syndrome/MPN overlap), their recognition is essential given the exquisite sensitivity of such cases to imatinib.…”

Section: Terminology and Classificationmentioning

confidence: 99%

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Gotlib¹,

2008

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“…23 RNA was reverse transcribed using random hexamer priming and MMLV reverse transcriptase (Invitrogen). Single-step and nested RT-PCR for the detection of FIP1L1-PDGFRA, 5 GIPIAP1-PDGFRB, 21 and MYO18A-PDGFRB 22 fusion genes was performed as previously described. Single-step primers for the detection of the SART3-PDGFRB fusion gene were SART2F: 5'-CTGATTATGTGGAGATTTGGCA-3', and PDGFR-C 5'-TGGCTTCTTCTGCCAAAGCA-3'.…”

Section: Rna Extraction Cdna Synthesis and Reverse Transcriptase Polmentioning

confidence: 99%

Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis

Erben¹,

Gosenca²,

Müller³

et al. 2010

Haematologica

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BackgroundRapid identification of diverse fusion genes with involvement of PDGFRA or PDGFRB in eosinophilia-associated myeloproliferative neoplasms is essential for adequate clinical management but is complicated by the multitude and heterogeneity of partner genes and breakpoints. Design and MethodsWe established a generic quantitative reverse transcriptase polymerase chain reaction to detect overexpression of the 3'-regions of PDGFRA or PDGFRB as a possible indicator of an underlying fusion. ResultsAt diagnosis, all patients with known fusion genes involving PDGFRA (n=5; 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 versus 0.0066 versus 0.0064, P<0.0001; PDGFRB/ABL: 196 versus 3.8 versus 5.85, P<0.0001). The sensitivity and specificity of the activation screening test were, respectively, 100% and 88.4% for PDGFRA and 100% and 94% for PDGFRB. Furthermore, significant overexpression of PDGFRB was found in a patient with an eosinophilia-associated myeloproliferative neoplasm with uninformative cytogenetics and an excellent response to imatinib. Subsequently, a new SART3-PDGFRB fusion gene was identified by 5´-rapid amplification of cDNA ends polymerase chain reaction (5'-RACE-PCR). ConclusionsQuantitative reverse transcriptase polymerase chain reaction analysis is a simple and useful adjunct to standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in eosinophilia-associated myeloproliferative neoplasms or related disorders. © F e r r a t a S t o r t i F o u n d a t i o n

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Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor gene

Cited by 86 publications

References 44 publications

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis

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