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- Hultdin, Magnus, et al.
(författare)
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Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications
- 2003
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 88:4, s. 593-598
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Tidskriftsartikel (refereegranskat)abstract
- The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (> 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.
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- Rosenquist, R, et al.
(författare)
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Clonal evolution as judged by immunoglobulin heavy chain gene rearrangements in relapsing precursor-B acute lymphoblastic leukemia.
- 1999
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Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 63:3, s. 171-9
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Tidskriftsartikel (refereegranskat)abstract
- Oligoclonality and ongoing clonal evolution are common features in patients with precursor-B (pre-B) acute lymphoblastic leukemia (ALL), as judged by immunoglobulin heavy chain (IgH) gene rearrangement analysis. These features are considered to be results of secondary rearrangements after malignant transformation or emergence of new tumor clones. In the present study we analyzed the IgH gene rearrangement status in 18 cases with relapsing pre-B ALL using variable heavy chain (V(H)) gene family specific polymerase chain reaction (PCR) amplification and single stranded conformation polymorphism (SSCP) analysis. Clonal IgH rearrangements were displayed in all leukemias but one, and altered rearrangement patterns occurred in five cases (29%), which were selected for detailed nucleotide sequence analysis. In one case, multiple subclones at diagnosis were suggested to be derived from a progenitor clone through joining of different V(H) germline gene segments to a pre-existing D-J(H) complex (V(H) to D-J(H) joining). Evidence for V(H) gene replacement with identical N-sequences at the V(H)-D junction and a common D-J(H) region was observed in one case. Diversification at the V(H)-D junction consisting of heterogeneous N-sequences were observed in one case. This molecular modification of the V(H)-D region could fit a hypothesized "open-and-shut" mechanism. Nevertheless, despite these ongoing events at least one IgH rearrangement remained unchanged throughout the disease in most patients, indicating that the immunoglobulin heavy chain locus can be a suitable marker for detection of minimal residual disease (MRD).
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