Changing antigen receptor gene rearrangements in a case of early pre-B cell leukemia: Evidence for a tumor progenitor cell with stem cell features and implications for monitoring residual disease

TY - JOUR

T1 - Changing antigen receptor gene rearrangements in a case of early pre-B cell leukemia

T2 - Evidence for a tumor progenitor cell with stem cell features and implications for monitoring residual disease

AU - Tycko, Benjamin

AU - Ritz, Jerome

AU - Sallan, Stephen

AU - Sklar, Jeffrey

PY - 1992/1/15

Y1 - 1992/1/15

N2 - A case of acute lymphoblastic leukemia (ALL) was encountered in which the two clonal γ T-cell receptor gene (TCRγ) rearrangements found in bone marrow (BM) samples at relapse both differed from the single clonal TCRγ rearrangement present in BM obtained at diagnosis 5 years previously. In contrast, two clonal Ig heavy chain gene (IgH) rearrangements present at relapse were identical to those present at diagnosis. Comparison of the DNA sequences of the relapse TCRγ rearrangements with that of the diagnostic TCRγ rearrangement indicated that they must have been generated de novo from TCRγ loci in germline configuration. By polymerase chain reaction using clonotypic N-region oligonucleotide primers (N-PCR), cells bearing the diagnosis or relapse TCRγ rearrangements were undetectable in the sample from the opposite time point. Two BM samples obtained at different times in clinical remission were both devoid of detectable residual tumor when analyzed by N-PCR, indicating a depth of remission of less than 1 tumor cell per 4 × 105 BM mononuclear cells. The tumor cells showed a primitive phenotype: T-cell antigen-negative, CALLA/CD10-negative, CD20-negative, CD19-positive, and positive for the myeloid marker My9. This case, which appears to represent a tumor arising from a progenitor cell with both early B-lineage and certain stem cell features, has implications for monitoring residual ALL and possibly also for treatment of the disease.

AB - A case of acute lymphoblastic leukemia (ALL) was encountered in which the two clonal γ T-cell receptor gene (TCRγ) rearrangements found in bone marrow (BM) samples at relapse both differed from the single clonal TCRγ rearrangement present in BM obtained at diagnosis 5 years previously. In contrast, two clonal Ig heavy chain gene (IgH) rearrangements present at relapse were identical to those present at diagnosis. Comparison of the DNA sequences of the relapse TCRγ rearrangements with that of the diagnostic TCRγ rearrangement indicated that they must have been generated de novo from TCRγ loci in germline configuration. By polymerase chain reaction using clonotypic N-region oligonucleotide primers (N-PCR), cells bearing the diagnosis or relapse TCRγ rearrangements were undetectable in the sample from the opposite time point. Two BM samples obtained at different times in clinical remission were both devoid of detectable residual tumor when analyzed by N-PCR, indicating a depth of remission of less than 1 tumor cell per 4 × 105 BM mononuclear cells. The tumor cells showed a primitive phenotype: T-cell antigen-negative, CALLA/CD10-negative, CD20-negative, CD19-positive, and positive for the myeloid marker My9. This case, which appears to represent a tumor arising from a progenitor cell with both early B-lineage and certain stem cell features, has implications for monitoring residual ALL and possibly also for treatment of the disease.

UR - https://www.scopus.com/pages/publications/0026514149

M3 - Article

C2 - 1309670

SN - 0006-4971

VL - 79

SP - 481

EP - 488

JO - Blood

JF - Blood

IS - 2

ER -