Effect of the hemoregulatory peptide (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 and MIP-1 alpha is reduced in bone marrow cultures from patients with chronic myeloid leukemia (CML)
H. Karlic et al., Effect of the hemoregulatory peptide (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 and MIP-1 alpha is reduced in bone marrow cultures from patients with chronic myeloid leukemia (CML), STEM CELLS, 19(4), 2001, pp. 321-328
The granulocyte-derived hemoregulatory peptide pyroGlu-Glu-Asp-Cys-Lys = pE
EDCK is known to keep hematopoietic cells quiescent. When oxidized to its d
imeric form (pEEDCK)2, it activates growth of hematopoietic progenitors in
association with stroma derived cytokines, (pEEDCK)2 has a Cys-Cys motif wh
ich is also a typical feature of the macrophage inflammatory protein (MIP-1
alpha). The present study was designed to analyze differences between the
response of normal and leukemic progenitor cells to (pEEDCK)2 or MIP-1 alph
a. When long-term bone marrow cultures (LTBMCs) were incubated with (pEEDCK
)2 or MIP-1 alpha and/or cytokines, the stimulatory effect on colony-formin
g units-granulocyte/erythroid/macrophage/megakaryocyte of LTBMC from chroni
c myeloid leukemia (CML) patients was less than 50% compared to LTBMC from
healthy humans. No difference in oncogene expression could be observed in L
TBMC from CML patients regarding reduction of Philadelphia chromosome-assoc
iated transcription of the BCR-ABL gene. With respect to the expression of
growth and differentiation-associated genes (G alpha 16, 5-lipoxygenase, ph
ospholipaseA2, c-kit, and CD34), which were analyzed from LTBMC by semiquan
titative reverse transcriptase-polymerase chain reaction, the same transcri
ption rate was observed in CML patients and healthy donors. However, two is
oforms of a key enzyme of oxidative metabolism, carnitine palmitoyltransfer
ase (CPT1A and CPT1B), showed 50-fold higher expression rates in LTBMC cell
s of healthy donors compared to CML patients.
It is known that a decrease in oxidative metabolism is associated with an i
ncrease in redox equivalents in malignancy. This might result in a reductio
n of disulphide bonds in (pEEDCK)2 or MIP-1 alpha, thus inducing a downregu
lation of these factors in bone marrow from CML patients.