Effect of the Hemoregulatory Peptide (pEEDCK)2 (pyroGlu‐Glu‐Asp‐Cys‐Lys)2 and MIP‐1α is Reduced in Bone Marrow Cultures from Patients with Chronic Myeloid Leukemia (CML)

The granulocyte‐derived hemoregulatory peptide pyroGlu‐Glu‐Asp‐Cys‐Lys = pEEDCK is known to keep hematopoietic cells quiescent. When oxidized to its dimeric form (pEEDCK)2, it activates growth of hematopoietic progenitors in association with stroma‐derived cytokines. (pEEDCK)2 has a Cys‐Cys motif which is also a typical feature of the macrophage inflammatory protein (MIP‐1α). The present study was designed to analyze differences between the response of normal and leukemic progenitor cells to (pEEDCK)2 or MIP‐1α. When long‐term bone marrow cultures (LTBMCs) were incubated with (pEEDCK)2 or MIP‐1α and/or cytokines, the stimulatory effect on colony‐forming units‐granulocyte/erythroid/macrophage/megakaryocyte of LTBMC from chronic myeloid leukemia (CML) patients was less than 50% compared to LTBMC from healthy humans. No difference in oncogene expression could be observed in LTBMC from CML patients regarding reduction of Philadelphia chromosome‐associated transcription of the BCR‐ABL gene. With respect to the expression of growth and differentiation‐associated genes (Gα16, 5‐lipoxygenase, phospholipaseA2, c‐kit, and CD34), which were analyzed from LTBMC by semiquantitative reverse transcriptase‐polymerase chain reaction, the same transcription rate was observed in CML patients and healthy donors. However, two isoforms of a key enzyme of oxidative metabolism, carnitine palmitoyltransferase (CPT1A and CPT1B), showed 50‐fold higher expression rates in LTBMC cells of healthy donors compared to CML patients.