Showing papers on "Friend leukemia published in 2014"

Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation

Abstract: Point mutations in the 5′ UTR of ankyrin repeat domain 26 (ANKRD26) are associated with familial thrombocytopenia 2 (THC2) and a predisposition to leukemia. Here, we identified underlying mechanisms of ANKRD26-associated thrombocytopenia. Using megakaryocytes (MK) isolated from THC2 patients and healthy subjects, we demonstrated that THC2-associated mutations in the 5′ UTR of ANKRD26 resulted in loss of runt-related transcription factor 1 (RUNX1) and friend leukemia integration 1 transcription factor (FLI1) binding. RUNX1 and FLI1 binding at the 5′ UTR from healthy subjects led to ANKRD26 silencing during the late stages of megakaryopoiesis and blood platelet development. We showed that persistent ANKRD26 expression in isolated MKs increased signaling via the thrombopoietin/myeloproliferative leukemia virus oncogene (MPL) pathway and impaired proplatelet formation by MKs. Importantly, we demonstrated that ERK inhibition completely rescued the in vitro proplatelet formation defect. Our data identify a mechanism for development of the familial thrombocytopenia THC2 that is related to abnormal MAPK signaling.

Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass and its confirmation by demonstration of EWS/friend leukemia integration 1 fusion gene.

Abstract: Ewing's sarcoma (EWS) is an undifferentiated sarcoma of bone. Its morphologic appearance resembles many other malignant small round cell tumors. Due to the morphologic overlap, there is diagnostic difficulty and for accurate diagnosis, requires special studies such as immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. We report a case of metastatic EWS from orbital mass in a 14-year-old female child diagnosed by cytology after clinicopathologic evaluation. She presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall. Cytosmear and Tru-cut biopsy was taken from the orbital mass showed features of EWS. It was confirmed later by further studies including demonstration of EWS/friend leukemia integration-1 fusion gene by molecular genetic analysis.

Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass and its confi rmation by demonstration of EWS/friend leukemia and its confi rmation by demonstration of EWS/friend leukemia

Abstract: Ewing's sarcoma (EWS) is an undifferentiated sarcoma of bone. Its morphologic appearance resembles many other malignant small round cell tumors. Due to the morphologic overlap, there is diagnostic diffi culty and for accurate diagnosis, requires special studies such as immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. We report a case of metastatic EWS from orbital mass in a 14-year-old female child diagnosed by cytology after clinicopathologic evaluation. She presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall. Cytosmear and Tru-cut biopsy was taken from the orbital mass showed features of EWS. It was confi rmed later by further studies including demonstration of EWS/friend leukemia integration-1 fusion gene by molecular genetic analysis.