Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia

Int J Hematol. 2018 Sep;108(3):274-281. doi: 10.1007/s12185-018-2472-9. Epub 2018 May 29.

Abstract

The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells. We consecutively evaluated the ratio of t(15;17)-positive cells using fluorescence in situ hybridization in eight newly diagnosed patients with APL. We confirmed the differentiation of APL cells until cytogenetic complete remission; the association of a decrease of t(15;17)-positive NPMs and an increase of t(15;17)-positive PMNs was followed by a decrease of t(15;17)-positive PMNs. The kinetic pattern of t(15;17)-positive NPMs and PMNs was consistent in most patients, irrespective of leukocyte counts at diagnosis, additional chromosomal changes, and ATRA with or without chemotherapies. Kinetic analysis enables us to evaluate treatment response and the recovery of normal hematopoiesis in individuals.

Keywords: Early death; Fluorescence in situ hybridization; PML–RARA; t(15;17).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Transformation, Neoplastic
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotype
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / pathology*
  • Male
  • Middle Aged
  • Promyelocytic Leukemia Protein / genetics
  • Retinoic Acid Receptor alpha / genetics
  • Translocation, Genetic
  • Tretinoin / therapeutic use*

Substances

  • Promyelocytic Leukemia Protein
  • RARA protein, human
  • Retinoic Acid Receptor alpha
  • PML protein, human
  • Tretinoin