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Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection.
Haematologica. 1998 Dec; 83(12):1069-75.H

Abstract

BACKGROUND AND OBJECTIVE

Normal B-cell differentiation has been characterized extensively, but discrepancies persist regarding the exact sequence of antigen expression. Few systematic studies focusing on identification of the minor or undetectable B-cell subsets in normal human bone marrow (BM) which are frequently found in leukemic cells have been performed. Such studies could help to monitor minimal residual disease (MRD) in precursor-B-acute lymphoblastic leukemia (precursor-B-ALL). The aim of the present study was to analyze the sequence of antigen expression among normal human CD19+ B cells from adult BM. Our major goal was to identify infrequent and undetectable B-cell phenotypes that could be used for the detection of MRD in patients with precursor-B-ALL.

DESIGN AND METHODS

Adult BM samples from a total of 33 healthy volunteers were analyzed using triple stainings, and measured by flow cytometry. A sensitive method based on the two-step acquisition procedure was used for the identification and characterization of cells present at very low frequencies.

RESULTS

Five different subsets of CD19+ cells were identified in normal BM samples according to their degree of maturation: 1) CD19+/CD34+/CD10-/CD20-/CD22dlm+ (0.5 +/- 0.4% B cells); 2) CD19+/CD34-/CD10++/CD20-/CD22dlm+ (3.4 +/- 2.7%); 3) CD19+/CD34-/CD10+/CD20-/CD22dlm+ (3.5 +/- 2.2%); 4) CD19+/CD34-/CD10+/CD20+,++/CD22dlm+ (21 +/- 11%), and 5) CD19+/CD34-/CD10-/CD20++/CD22+ (73 +/- 19%). We observed that several B-cell phenotypes are frequent among precursor-B-ALL, but are infrequent or undetectable in normal human B cell differentiation. Accordingly, in all normal BM samples analyzed, less than 4 x 10(-5) cells co-expressed CD19 and CD117; CD20strong+/CD34+ and CD22strong+/CD34+ events were found at frequencies less than 5 x 10(-4), while CD20+/CD34+ phenotypes were found in less than 1 x 10(-3) BM cells. Although both CD19+/CD13+ and CD19+/CD33+ events were found at frequencies of up to 3 x 10(-3), they never formed a well-defined population of cells and therefore these latter phenotypic patterns could also be of use for MRD investigation in CD13+ and/or CD33+ precursor-B-ALL cases.

INTERPRETATION AND CONCLUSIONS

Our results show that in adult BM normal B-cells display constant patterns of maturation as regards both their phenotypic characteristics and their relative distribution. Abnormalities in these patterns provide a potentially useful tool for monitoring MRD in precursor-B-ALL patients who achieve cytomorphologic complete remission.

Authors+Show Affiliations

Servicio General de Citometría, University of Salamanca, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9949623

Citation

Ciudad, J, et al. "Immunophenotypic Analysis of CD19+ Precursors in Normal Human Adult Bone Marrow: Implications for Minimal Residual Disease Detection." Haematologica, vol. 83, no. 12, 1998, pp. 1069-75.
Ciudad J, Orfao A, Vidriales B, et al. Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. Haematologica. 1998;83(12):1069-75.
Ciudad, J., Orfao, A., Vidriales, B., Macedo, A., Martínez, A., González, M., López-Berges, M. C., Valverde, B., & San Miguel, J. F. (1998). Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. Haematologica, 83(12), 1069-75.
Ciudad J, et al. Immunophenotypic Analysis of CD19+ Precursors in Normal Human Adult Bone Marrow: Implications for Minimal Residual Disease Detection. Haematologica. 1998;83(12):1069-75. PubMed PMID: 9949623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. AU - Ciudad,J, AU - Orfao,A, AU - Vidriales,B, AU - Macedo,A, AU - Martínez,A, AU - González,M, AU - López-Berges,M C, AU - Valverde,B, AU - San Miguel,J F, PY - 1999/2/9/pubmed PY - 1999/2/9/medline PY - 1999/2/9/entrez SP - 1069 EP - 75 JF - Haematologica JO - Haematologica VL - 83 IS - 12 N2 - BACKGROUND AND OBJECTIVE: Normal B-cell differentiation has been characterized extensively, but discrepancies persist regarding the exact sequence of antigen expression. Few systematic studies focusing on identification of the minor or undetectable B-cell subsets in normal human bone marrow (BM) which are frequently found in leukemic cells have been performed. Such studies could help to monitor minimal residual disease (MRD) in precursor-B-acute lymphoblastic leukemia (precursor-B-ALL). The aim of the present study was to analyze the sequence of antigen expression among normal human CD19+ B cells from adult BM. Our major goal was to identify infrequent and undetectable B-cell phenotypes that could be used for the detection of MRD in patients with precursor-B-ALL. DESIGN AND METHODS: Adult BM samples from a total of 33 healthy volunteers were analyzed using triple stainings, and measured by flow cytometry. A sensitive method based on the two-step acquisition procedure was used for the identification and characterization of cells present at very low frequencies. RESULTS: Five different subsets of CD19+ cells were identified in normal BM samples according to their degree of maturation: 1) CD19+/CD34+/CD10-/CD20-/CD22dlm+ (0.5 +/- 0.4% B cells); 2) CD19+/CD34-/CD10++/CD20-/CD22dlm+ (3.4 +/- 2.7%); 3) CD19+/CD34-/CD10+/CD20-/CD22dlm+ (3.5 +/- 2.2%); 4) CD19+/CD34-/CD10+/CD20+,++/CD22dlm+ (21 +/- 11%), and 5) CD19+/CD34-/CD10-/CD20++/CD22+ (73 +/- 19%). We observed that several B-cell phenotypes are frequent among precursor-B-ALL, but are infrequent or undetectable in normal human B cell differentiation. Accordingly, in all normal BM samples analyzed, less than 4 x 10(-5) cells co-expressed CD19 and CD117; CD20strong+/CD34+ and CD22strong+/CD34+ events were found at frequencies less than 5 x 10(-4), while CD20+/CD34+ phenotypes were found in less than 1 x 10(-3) BM cells. Although both CD19+/CD13+ and CD19+/CD33+ events were found at frequencies of up to 3 x 10(-3), they never formed a well-defined population of cells and therefore these latter phenotypic patterns could also be of use for MRD investigation in CD13+ and/or CD33+ precursor-B-ALL cases. INTERPRETATION AND CONCLUSIONS: Our results show that in adult BM normal B-cells display constant patterns of maturation as regards both their phenotypic characteristics and their relative distribution. Abnormalities in these patterns provide a potentially useful tool for monitoring MRD in precursor-B-ALL patients who achieve cytomorphologic complete remission. SN - 0390-6078 UR - https://www.unboundmedicine.com/medline/citation/9949623/Immunophenotypic_analysis_of_CD19+_precursors_in_normal_human_adult_bone_marrow:_implications_for_minimal_residual_disease_detection_ L2 - http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=9949623 DB - PRIME DP - Unbound Medicine ER -