Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.
Recurrent anomalies of the short arm of chromosome 9, including interstitial deletions and translocations, have often been described. Recently two cyclin-dependent kinase inhibitors, known as P16 (INK4A/MTS1) and P15 (INK4B/MTS2), which map to 9p21, have been found deleted in a wide range of tumors and particularly in leukemic cells. We report here Southern blot analyses of cyclin-dependent kinase inhibitors (P16, P15, P21, and P27) status in primary tumoral cells of 121 patients with acute lymphoblastic leukemias, 85 patients with acute myeloid leukemias and 42 patients with B-chronic lymphocytic leukemias. P16 inactivation was found in 25 of 38 T-ALLs and in 28 of 83 B-lineage ALLs. In eight cases (three T-ALLs and five B-lineage ALLs), one or both alleles of P16 locus were rearranged. In these cases, breakpoints occurred within the two major breakpoints cluster regions previously described in T-ALLs. Homozygous P16 deletions were observed in two of 85 AMLs but in none of the 42 B-CLL cases tested. Our results suggest that P16 inactivation are the most frequent event observed in ALL (44%), are quite rare in AML (<2%) and seem to be absent in CLL. Search for P27 and P21 deletion was negative in B/T-lineage ALLs and monoallelic deletions of P27 were found in four AML cases (5%).
Hayette
S
S
Laboratoire d'Hématologie et de Cytogénétique, Hôpital Edouard Herriot, Lyon, France.
Thomas
X
X
Bertrand
Y
Y
Tigaud
I
I
Callanan
M
M
Thiebaut
A
A
Charrin
C
C
Archimbaud
E
E
Magaud
J P
JP
Rimokh
R
R
D000328:Adult; D000483:Alleles; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D006720:Homozygote; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics; D015458:Leukemia, T-Cell / Q000196:embryology / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins