A Surrogate Marker Profile for PML/RARα Expressing Acute Promyelocytic Leukemia and the Association of Immunophenotypic Markers with Morphologic and Molecular Subtypes

Elisabeth M. Paietta, O. Goloubeva, D. Neuberg, J. M. Bennett, R. Gallagher, Janis Racevskis, G. Dewald, P. H. Wiernik, M. S. Tallman

Research output: Contribution to journalArticle

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Abstract

Background: The availability of genotype-specific therapy for PML/RARαpos acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DRlow, CD34low, P-glycoproteinlow myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/ RARα fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DRlow, CD11alowL subunit of the leukocyte integrin LFA-1), CD18 low2 subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (αM leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARαpos APL cells typically lack leukocyte integrins. HLA-DRlow, CD11alow, CD18low is a reliable surrogate antigen expression profile for PML/RARαpos APL, irrespective of morphology and transcript isoform.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCytometry Part B - Clinical Cytometry
Volume59
Issue number1
StatePublished - May 2004

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Acute Promyelocytic Leukemia
Biomarkers
Integrins
Lymphocyte Function-Associated Antigen-1
Leukocytes
CD11b Antigens
CD45 Antigens
L Forms
Antigens
Neural Cell Adhesion Molecules
Granulocyte Precursor Cells
Viral Tumor Antigens
Acute Myeloid Leukemia
Protein Isoforms
Stem Cells
Fluorescence
Genotype

Keywords

  • APL
  • Multiparameter flow cytometry
  • PML/RARα
  • Surrogate immunophenotype
  • Transcript isoforms

ASJC Scopus subject areas

  • Hematology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Biophysics
  • Endocrinology

Cite this

A Surrogate Marker Profile for PML/RARα Expressing Acute Promyelocytic Leukemia and the Association of Immunophenotypic Markers with Morphologic and Molecular Subtypes. / Paietta, Elisabeth M.; Goloubeva, O.; Neuberg, D.; Bennett, J. M.; Gallagher, R.; Racevskis, Janis; Dewald, G.; Wiernik, P. H.; Tallman, M. S.

In: Cytometry Part B - Clinical Cytometry, Vol. 59, No. 1, 05.2004, p. 1-9.

Research output: Contribution to journalArticle

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abstract = "Background: The availability of genotype-specific therapy for PML/RARαpos acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DRlow, CD34low, P-glycoproteinlow myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/ RARα fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DRlow, CD11alow (αL subunit of the leukocyte integrin LFA-1), CD18 low (β2 subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (αM leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARαpos APL cells typically lack leukocyte integrins. HLA-DRlow, CD11alow, CD18low is a reliable surrogate antigen expression profile for PML/RARαpos APL, irrespective of morphology and transcript isoform.",
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T1 - A Surrogate Marker Profile for PML/RARα Expressing Acute Promyelocytic Leukemia and the Association of Immunophenotypic Markers with Morphologic and Molecular Subtypes

AU - Paietta, Elisabeth M.

AU - Goloubeva, O.

AU - Neuberg, D.

AU - Bennett, J. M.

AU - Gallagher, R.

AU - Racevskis, Janis

AU - Dewald, G.

AU - Wiernik, P. H.

AU - Tallman, M. S.

PY - 2004/5

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N2 - Background: The availability of genotype-specific therapy for PML/RARαpos acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DRlow, CD34low, P-glycoproteinlow myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/ RARα fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DRlow, CD11alow (αL subunit of the leukocyte integrin LFA-1), CD18 low (β2 subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (αM leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARαpos APL cells typically lack leukocyte integrins. HLA-DRlow, CD11alow, CD18low is a reliable surrogate antigen expression profile for PML/RARαpos APL, irrespective of morphology and transcript isoform.

AB - Background: The availability of genotype-specific therapy for PML/RARαpos acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DRlow, CD34low, P-glycoproteinlow myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/ RARα fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DRlow, CD11alow (αL subunit of the leukocyte integrin LFA-1), CD18 low (β2 subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (αM leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARαpos APL cells typically lack leukocyte integrins. HLA-DRlow, CD11alow, CD18low is a reliable surrogate antigen expression profile for PML/RARαpos APL, irrespective of morphology and transcript isoform.

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KW - PML/RARα

KW - Surrogate immunophenotype

KW - Transcript isoforms

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