| 1. |
- Li, Aihong, et al.
(författare)
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Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse : implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection.
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 102:13, s. 4520-4526
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements provide clonal markers useful for diagnosis and measurement of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We analyzed the sequences of Ig and TCR gene rearrangements obtained at presentation and relapse in 41 children with ALL to study clonal stability, which has important implications for monitoring MRD, during the course of the disease. In 42%, all original Ig and/or TCR sequences were conserved. In 24%, one original sequence was preserved but the other lost, and in 14% the original sequences were conserved with new sequences identified at relapse. In 20% only new sequences were found at relapse. Using primers designed from the novel relapse sequences, the relapse clone could be identified as subdominant clones in the diagnostic sample in 8 of 14 patients. Alteration of these clonal gene rearrangements is a common feature in childhood ALL. MRD detection should include multiple gene targets to minimize false-negative samples or include also multicolor flow cytometry. In some cases the leukemic progenitor cell might arise earlier in lineage before DHJH recombination but retain the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements.
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| 2. |
- Li, Aihong, et al.
(författare)
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Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia : implications for the mechanisms of VDJ recombination and for pathogenesis.
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 103:12, s. 4602-9
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Tidskriftsartikel (refereegranskat)abstract
- Sequence analysis of the immunoglobulin heavy chain genes (IgH) has demonstrated preferential usage of specific variable (V), diversity (D), and joining (J) genes at different stages of B-cell development and in B-cell malignancies, and this has provided insight into B-cell maturation and selection. Knowledge of the association between rearrangement patterns based on updated databases and clinical characteristics of pediatric acute lymphoblastic leukemia (ALL) is limited. We analyzed 381 IgH sequences identified at presentation in 317 children with B-lineage ALL and assessed the V(H)D(H)J(H) gene utilization profiles. The D(H)J(H)-proximal V(H) segments and the D(H)2 gene family were significantly overrepresented. Only 21% of V(H)-J(H) joinings were potentially productive, a finding associated with a trend toward an increased risk of relapse. These results suggest that physical location at the V(H) locus is involved in preferential usage of D(H)J(H)-proximal V(H) segments whereas D(H) and J(H) segment usage is governed by position-independent molecular mechanisms. Molecular pathophysiology appears relevant to clinical outcome in patients who have only productive rearrangements, and specific rearrangement patterns are associated with differences in the tumor biology of childhood ALL.
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