MYB deregulation from a EWSR1-MYB fusion at leukemic evolution of a JAK2 V617F positive primary myelofibrosis
| Autor: | Paolo Gorello, Fabrizia Pellanera, Roberta La Starza, Tamara Iannotti, Danika Di Giacomo, Gianluca Barba, Tiziana Pierini, Valentina Pierini, Anair Graciela Lema Fernandez, Franca Falzetti, Cristina Mecucci |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty IDH1 Leukemic transformation Case Report MYB Biology Biochemistry 03 medical and health sciences medicine Genetics Genetics(clinical) Myelofibrosis Molecular Biology Genetics (clinical) Biochemistry medical PMF Molecular Medicine Biochemistry (medical) Cytogenetics medicine.disease Molecular medicine Human genetics Transformation (genetics) 030104 developmental biology Cancer research JAK2 V617F |
| Zdroj: | Molecular Cytogenetics |
| Popis: | Background Although Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are usually not aggressive, the type and the number of molecular lesions impact greatly on leukemic transformation. Indeed, the molecular background underlying progression is still largely unexplored even though ASXL1, IDH1/2, SRSF2, and TP53 mutations, together with adverse karyotypic changes, place the patient at high risk of leukemic transformation. Case presentation Our patient, a 64-year old man with a diagnosis of JAK2V617F primary myelofibrosis (PMF) had an unusually rapid leukemic transformation. Genomic profiling showed that TET2 and SRSF2 mutations were also present. At leukemic transformation, the patient developed a complex chromosome rearrangement producing a EWSR1-MYB fusion. Remarkably, the expression of MYB and of its target BCL2 was, respectively, ≥4.7 and ≥2.8 fold higher at leukemic transformation than after chemotherapy, when the patient obtained the hematological remission. At this time point, the EWSR1-MYB fusion disappeared while JAK2V617F, TET2, and SRSF2 mutations, as well as PMF morphological features persisted. Conclusions Rapid leukemic transformation of JAK2V617F PMF was closely linked to a previously undescribed putative EWSR1-MYB transcription factor which was detected only at disease evolution. We hypothesize that the EWSR1-MYB contributed to leukemia transformation through at least two mechanisms: 1) it sustained MYB expression, and consequently deregulated its target BCL2, a putative onco-suppressor gene; and 2) ectopic EWSR1-MYB expression probably fulfilled its own oncogenic potential as demonstrated for other MYB-fusions. As our study confirmed that MYB is recurrently involved in chronic as well as leukemic transformation of PMF, it appears to be a valid molecular marker for tailored treatments. Electronic supplementary material The online version of this article (doi:10.1186/s13039-016-0277-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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