Clonal selection in acute lymphoblastic leukaemia demonstrated by polymerase chain reaction analysis of immunoglobulin heavy chain and T-cell receptor delta chain rearrangements.
Immunoglobulin heavy chain (IgH) and T-cell receptor (TcR) genes can be monitored as markers of clonality by polymerase chain reaction (PCR) analysis in acute lymphoblastic leukaemia (ALL). We report the short clinical course of a 16-year-old patient with ALL and a t(4;11) who relapsed early following treatment and subsequently received reinduction chemotherapy followed by peripheral blood stem cell transplantation with interleukin 2 therapy. Despite this, the patient relapsed and died 8 months after presentation. The leukaemic cells were analysed by PCR and showed rearrangements of TcR V delta 2-D delta 3 and IgH CDRIII genes. Direct sequence analysis of the TcR delta and IgH PCR products revealed two leukaemic clones at diagnosis with one present at minimal levels. After initial therapy the major clone was no longer detected even in subsequent relapse samples but the originally minimal clone persisted and increased despite further treatment, indicating drug resistance.
Department of Haematology, Royal Infirmary, Edinburgh, UK.
K
K
Langlands
J I
JI
Craig
R S
RS
Anthony
A C
AC
Parker
D000293:Adolescent; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D002999:Clone Cells; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D009838:Oligodeoxyribonucleotides; D016692:Receptors, Antigen, T-Cell, gamma-delta