Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRB, p16INK4A) in childhood acute lymphoblastic leukemia.
Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclin-dependent kinases (cdk2, cdk4) and tumor-suppressor genes (pRb, p16INK4A), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse-free-intervals or the frequency of recurrence in patients. Children with cdk4-positive ALL had a lower probability of remaining in first continuous remission than children with cdk4-negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance.
Volm
M
M
Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg.
Koomägi
R
R
Stammler
G
G
Rittgen
W
W
Zintl
F
F
Sauerbrey
A
A
D000293:Adolescent; D042846:CDC2-CDC28 Kinases; D002648:Child; D002675:Child, Preschool; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000032:analysis*; D016213:Cyclins / Q000032:analysis*; D005260:Female; D016161:Genes, Retinoblastoma; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins
D016213:Cyclins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases