4 / 15
Page 26
Notes:
allied
academies
August 23-24, 2018 | London, UK
Hematology and Oncology
2
nd
International Conference on
Journal of Hematology and Blood Disorder | Volume 2
Imbalanced proportions of phospatidylinositol and phosphatidylcholine in plasma membranes of
hematopoietic cells in patients with paroxysmal nocturnal hemoglobinuria
Jacek Nowak
Institute of Hematology and Transfusion Medicine, Poland
P
aroxysmal nocturnal hemoglobinuria (PNH) is caused
by somatic mutation in phosphatidylinositol glycan
complementation group A (PIG-A) gene in single hematopoietic
stem/progenitor cell (HSC). Pathomechanism of clonal
domination of mutated HSCs over normal HSCs is not fully
clear including autoimmune, pro-survival and/or anti-apoptotic
background, among else. Phosphatidylinositol (PI) is important
anti-apoptotic second messenger in cells and its conversion to
glycosylated PI (GPI) is arrested in PIG-A mutated PNH cells. PI
content in cells is fine regulated by highly specific enzyme, the
phosphatidylinositol transfer protein that is able to deliver PI
to plasma membranes at the expense of equimolar quantity
of phosphatidylcholine (PC). In this study we assessed contents
of PI and PC phospholipids in nucleated hematopoietic cells
in patients with PNH (N=22) and healthy controls (N=6).
Phospholipid fractions were isolated from plasma membranes
using modified Folch-based lipid extraction protocol and
evaluated using high performance liquid chromatography
(HPLC) with charged aerosol detection (CAD). Phospholipid
contents were expressed as nmoles/10^6 cells to show
molecular proportions of PI and PC in cellular membranes. We
found significantly higher PI/PC molar ratio in PNH patients
than in controls both in polymorphonulear (PMN) (Mean±SE:
16.3±2.6 vs. 8.0±2.0 %mol/mol, p=0.020) and mononuclear
cell (MNC) fractions (20.5±3.8 vs. 9.6±2.7 %mol/mol, p=0.024).
This PI/PC imbalance was caused mainly by the fall of absolute
content of PC in cellular membranes in PNH patients. FLAER(-)
cell proportion in PNH patients correlated with PC content in
PMN cells (R=0.53, p=0.020). In PNH patients we found highly
significant correlation of platelet cell (PLT) counts with PC
content in MNC subset (R=0.55, p<0.01). Both white blood cell
(WBC) and PLT counts in patients show trend toward lower
values with increasing PI/PC molar ratios (R>0.39, p<0.09).
The results suggest that i) in PNH patients the proportions of
PI to PC molecules in plasma membranes of hematopoietic
cells are imbalanced. Higher relative proportions of PI may
potentially increase anti-apoptotic capacity of certain PI-
dependent enzymes in hematopoietic cells. ii) The results
suggest a protective role of PC in platelet aggregation and
turnover. In PNH patients PC deficiency in circulating blood
cells may be associated with increased risk of thrombosis.
Speaker Biography
Jacek Nowak has completed his PhD from Military Medical Academy, Łodz, Poland and
habilitation degree from Institute of Hematology and Transfusion Medicine, Warsaw,
Poland. He is the tenure professor and head of Department of Immunogenetics
at the Institute of Hematology and Transfusion Medicine. He has over 80
publications that have been cited over 470 times, and his publication H-index is 11
and has been serving as an editor at 2 books and has over 20 published chapters.
e:
jnowak@ihit.waw.pl