Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: Premature chromosome condensation/fluorescence in situ hybridization analysis Journal Article


Authors: Vyas, R. C.; Frankel, S. R.; Agbor, P.; Miller, W. H. Jr; Warrell, R. P. Jr; Hittelman, W. N.
Article Title: Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: Premature chromosome condensation/fluorescence in situ hybridization analysis
Abstract: The response of acute promyelocytic leukemia(APL) peripheral blood and bone marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during RA treatment using the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH). Before treatment, the predominant immature bone marrow cells were found to have t(15;17), whereas the residual mature granulocytes were diploid and lacked evidence of the translocation. In response to RA treatment, on increase in the leukocyte count was noted. The majority of these cells exhibited a t(15;17). Subsequently (eg, between days 5 and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The appearance of t(15;17) in gradually maturing elements suggests that RA contributed to a release of the maturation block of the leukemic elements. As responding patients obtained complete remission, diploid elements without evidence of the translocation prevailed in the blood and bone marrow. In 16 patients studied after 1 month in complete remission, all but 2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days later in 1 patient, whereas the second patient exhibited clinical evidence of relapse 20 days later. These results suggest that response of patients with APL to RA is associated with maturation, subsequent loss of the mature leukemic elements, and preferential regeneration of normal diploid hematopoietic elements. (C) 1996 by The American Society of Hematology.
Keywords: dna; diagnosis; cells; differentiation therapy; rar-alpha; hl-60; alpha gene; t(15-17) translocation; fuses
Journal Title: Blood
Volume: 87
Issue: 1
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1996-01-01
Start Page: 218
End Page: 226
Language: English
ACCESSION: WOS:A1996TN44100026
PROVIDER: wos
PUBMED: 8547645
DOI: 10.1182/blood.V87.1.218.218
Notes: Article -- Source: Wos
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  1. Raymond P Warrell
    175 Warrell
  2. Wilson H. Miller Jr
    48 Miller
  3. Stanley R. Frankel
    13 Frankel