Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene.
We have analyzed the molecular genetics of the breakpoints involved in the t(8;14) and t(14;18) translocations of an acute pre-B-cell leukemia from a patient with a history of follicular lymphoma. In this patient's leukemic cells, the breakpoint of the t(14;18) translocation occurred in the major breakpoint-cluster region of the BCL2 gene and became linked to the JH4 joining-region gene segment of the immunoglobulin heavy-chain locus on the 14q+ chromosome as previously observed in follicular lymphoma. An N region and heptamer and nonamer signal sequences indicated that this translocation occurred as a mistake in VH-DH-JH joining (where VH and DH are the variable and diversity segments). In the t(8;14) translocation, the breakpoint was located immediately 5' of the first exon of the MYC protooncogene, which was juxtaposed with the C gamma 2 constant gene segment of the second 14q+ chromosome. The finding of repeated sequences typical of switch regions suggested that this translocation occurred during heavy-chain isotype switching, resulting in progression to pre-B-cell leukemia with both the t(8;14) and the t(14;18) translocations. The terminal deoxynucleotidyltransferase-positive phenotype of the patient's leukemic cells further suggests that the pre-B-cell leukemia was derived from a pre-B cell carrying a t(14;18) translocation in the original follicular lymphoma. The polymerase chain reaction method was then used to identify cancer cells in the bone marrow of the patient.
Gauwerky
C E
CE
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Haluska
F G
FG
Tsujimoto
Y
Y
Nowell
P C
PC
Croce
C M
CM
D001483:Base Sequence; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011289:Preleukemia / Q000235:genetics*; D015183:Restriction Mapping