Konference: 2007 49th ASH Annual Meeting - účast ČR
Maligní lymfomy a leukémie
Číslo abstraktu: 1549
Autoři: RNDr. Hana Bruchová Votavová, Ph.D.; Donghoon Yoon; Dr. Archana M. Agarwal, MBBS; Ing. Eva Ratajová (Otáhalová); Hyojin Kim; MD Josef T. Prchal
Erythroid differentiation is a dynamic process leading to the
production of mature red blood cells. Even small variations in this
process may result in severe disease phenotype. To study this
process, we used a three-phase erythroid expansion system to expand
homogeneous erythroid progenitors (EPs) from peripheral blood
mononuclear cells (PB-MNCs) (Bruchova H. et al, 2007, Exp.
Hematology, in press). We then characterized the expanded EPs from
polycythemia vera (PV) patients and healthy donors at various
points of maturation comparing cell proliferation and
differentiation stage. EPs from PV patients outgrew controls up to
day 14 (12 fold for PV and 4 fold for control compared to day 1).
Differentiation was analyzed using both FACS analysis (with
CD71/CD235a staining) and morphological evaluation (Wright-Giemsa
staining), and demonstrated a more rapid differentiation of PV EPs
when compared to controls up to day 14. We then evaluated
apoptosis/cell cycle analysis by propidium iodide staining.
Although PV EPs contained larger S phase population (45%) than
controls (34%) at day 11, the apoptosis proportion of PV EPs was
increased 2 fold to control from day 14. To understand the
molecular mechanism of these differences between PV and controls,
we analyzed the gene expression of several known regulators in
erythropoiesis - BCL2, EPOR, cMYB, p27. Two transcripts (EPOR and
cMYB) showed unique profiles on PV EPs. The EPOR transcript
increased earlier in PV; i.e. from day 7 until day 21 and reached a
plateau at day 11, compared to day 9 until day 19 and plateau at
day 14 in controls. In addition, PV EPs contained higher levels of
EPOR transcripts than control on most of timepoints. Interestingly,
cMYB, which is known to augment early progenitor proliferation, was
highly expressed from day 7 in PV, through day 11. Control EPs also
expressed cMYB from day 9 through day 11; however, cMYB levels from
any stages of control EPs were markedly lower than PV EPs at day 7.
In this study, we demonstrate that PV erythropoiesis has unique
features of hyperproliferation and an accelerated differentiation.
These features are associated with earlier and higher expressions
of cMYB and EPOR at the early stage of erythropoiesis. # Both
authors are equally contributed to this work.
Abstract #1549 appears in Blood, Volume 110, issue 11, November 16,
Keywords: Polycythemia vera|c-myb|Erythropoietin Receptor
Disclosure: No relevant conflicts of interest to declare.
Saturday, December 8, 2007 5:30 PM
Session Info: Poster Session: Myeloproliferative Syndromes:
Biological (5:30 p.m.-7:30 p.m.)
Datum přednesení příspěvku: 8. 12. 2007