High mitochondrial membrane potential identifies patients with myeloproliferative neoplasms with a more aggressive natural history Meeting Abstract


Authors: Gardner, J. R.; Abdel-Wahab, O.; Frattini, M.; Jurcic, J. G.; Knapp, K.; Rosenblat, T. L.; Soff, G. A.; Levine, R.; Heaney, M.
Abstract Title: High mitochondrial membrane potential identifies patients with myeloproliferative neoplasms with a more aggressive natural history
Meeting Title: 52nd Annual Meeting of the American Society of Hematology (ASH)
Abstract: The myeloproliferative neoplasms (MPN) can have a variable natural history. Polycythemia vera and essential thrombocythemia, in particular, are conditions that can extend over decades, but some patients have clinical progression to Myelofibrosis or acute myeloid leukemia. As first articulated lay Warburg, cancers are metabolically distinguished from normal tissues by the use of glycolysis under aerobic conditions-To metabolically characterize the blood cells of patients with myeloproliferative neoplasms, we measured the mitochondrial membrane potential using the cyanine dye, JC-1. In examining cells derived from the blood and/or marrow of 159 patients with primary myelofibrosis, polycythemia vera and essential thrombocythemia; We found that this mitochondrial membrane potential (FL2/FL1=electrochemical potential/mitochondrial mass) was elevated compared to:the blood cells-of normal individuals. Thirty live percent of patients with polycythemia vera and essential thrombocythemia had normal MMP. In contrast, 97% of patients with primary myelofibrosis, post-polycythemia myelofibrosis, post-essential thrombocythemia myelofibrosis and acute myeloid leukemia following an MPN had evidence of cell populations with higher mitochondria,l membrane potential. Cells with distinctly higher mitochondrial Membrane potential could be indentified in platelets and polymorphonuclear leukocytes; however the MMP of. lymphocytes was normal, indicating that the alteration in, metabolic state likely occurred in a multipotential myeloid stem cell. Cell populations were confirmed by co-staining With anti-CD19, -CD45, -GlycophorinA and -beta 3-, integrin antibodies. Sequential analysis of patient samples found that the acquisition of higher mitochondrial membrane potential was stable and persistent over 2 years or more of follow up and that elevated membrane potential predisposed patients to disease progression. The balance of patients (65%) with ET had evidence of increased MMP suggesting the possibility of disease in an early state of evolution to a more aggressive condition. The increased MMP did not correlate with the presence of mutation in JAK2. These results indicate that clinically advanced MPN can be characterized by changes in mitochondrial physiology that might be identified non-invasively by flow cytometric staining with JC-1. In addition, the early nature of these changes may help to identify therapeutic targets.[GRAPHICS].
Keywords: mitochondrial membrane potential; cell population; electrochemical potential; disease possibility
Journal Title: Blood
Volume: 116
Issue: 21
Meeting Dates: 2010 Dec 4-7
Meeting Location: Orlando, FL
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-11-19
Start Page: 831
Language: English
ACCESSION: BIOSIS:PREV201100424535
PROVIDER: biosis
PUBMED: 22276300
Notes: --- - Meeting Abstract: 1992 - 52nd Annual Meeting of the American Society of Hematology (ASH) - Orlando, FL, USA - December 04 -07, 2010 - Amer Soc Hematol - "Source: Biosis"