Terminal transferase positive acute promyelocytic leukemia

In vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype

Elisabeth M. Paietta, J. P. Dutcher, P. H. Wiernik

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeolid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80%) and a lymphoid, TdT+ component (20%) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50% positive for VIM-D5 and OKT6, 30% positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70% of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1-associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.

Original languageEnglish (US)
Pages (from-to)107-114
Number of pages8
JournalBlood
Volume65
Issue number1
StatePublished - 1985

Fingerprint

Acute Promyelocytic Leukemia
DNA Nucleotidylexotransferase
Transferases
Phenotype
Muromonab-CD3
Antigens
T Lymphocyte Differentiation Antigens
Cells
CD3 Antigens
Isotretinoin
T-cells
Fluorescence microscopy
Retinoids
Conditioned Culture Medium
Tretinoin
Staining and Labeling
Immune Sera
In Vitro Techniques
Viral Tumor Antigens
Myeloid Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Terminal transferase positive acute promyelocytic leukemia : In vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype. / Paietta, Elisabeth M.; Dutcher, J. P.; Wiernik, P. H.

In: Blood, Vol. 65, No. 1, 1985, p. 107-114.

Research output: Contribution to journalArticle

@article{52c57175f8904168aa9f707769e6be29,
title = "Terminal transferase positive acute promyelocytic leukemia: In vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype",
abstract = "In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeolid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80{\%}) and a lymphoid, TdT+ component (20{\%}) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50{\%} positive for VIM-D5 and OKT6, 30{\%} positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70{\%} of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1-associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.",
author = "Paietta, {Elisabeth M.} and Dutcher, {J. P.} and Wiernik, {P. H.}",
year = "1985",
language = "English (US)",
volume = "65",
pages = "107--114",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Terminal transferase positive acute promyelocytic leukemia

T2 - In vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype

AU - Paietta, Elisabeth M.

AU - Dutcher, J. P.

AU - Wiernik, P. H.

PY - 1985

Y1 - 1985

N2 - In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeolid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80%) and a lymphoid, TdT+ component (20%) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50% positive for VIM-D5 and OKT6, 30% positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70% of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1-associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.

AB - In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeolid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80%) and a lymphoid, TdT+ component (20%) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50% positive for VIM-D5 and OKT6, 30% positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70% of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1-associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.

UR - http://www.scopus.com/inward/record.url?scp=0021962870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021962870&partnerID=8YFLogxK

M3 - Article

VL - 65

SP - 107

EP - 114

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -