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)

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
STEM CELLS
ISSN journal
1066-5099 → ACNP
Volume
19
Issue
4
Year of publication
2001
Pages
321 - 328
Database
ISI
SICI code
1066-5099(2001)19:4<321:EOTHP(>2.0.ZU;2-T
Abstract
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.