Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors.
Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non-c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low-expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.
Madsen
P S
PS
University Department of Medicine and Hematology, Aarhus Amtssygehus, Denmark.
Hokland
P
P
Clausen
N
N
Ellegaard
J
J
Hokland
M
M
D000293:Adolescent; D000361:Agammaglobulinemia / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D015180:Electrophoresis, Gel, Two-Dimensional; D015973:Gene Expression Regulation, Leukemic; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007239:Infections / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D007526:Isoelectric Point; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010766:Phosphorylation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000473:pathology; D000099190:MAP-Kinase-Activated Kinase 2
D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2