All-trans retinoic acid (ATRA) differentiates acute promyelocytic leukemia cells independently of P-glycoprotein (P-gp) related multidrug resistance

A. Takeshita, K. Shigeno, K. Shinjo, K. Naito, K. Ohnishi, H. Hayashi, M. Tanimoto, R. Ohno

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11 Citations (Scopus)


Here the relationship between all-trans retinoic acid (ATRA)-resistance and P-glycoprotein (P-gp)-associated multidrug resistance (MDR) is discussed in acute promyelocytic leukemia (APL). First, the remission rates of ATRA therapy are similar in relapsed/refractory APL to the preceding chemotherapy given and in newly diagnosed APL. Second, MDR1 cDNA-transduced NB4 (NB4/MDR) cells accumulate less Rhodamine-123 (Rh123) than NB4 cells, but there is no difference in the intracellular ATRA concentration between them. PSC833 or MS209, MDR modifiers, increases the intracellular accumulation of Rh123 in NB4/MDR and APL cells expressing P-gp, but not of ATRA. Third, the expression of CD11b, the NBT reduction activity, the proportion of apoptotic cells and the morphology are not different between NB4/MDR and NB4 cells, and between APL cells expressing P-gp and not. APL cells express little P-gp, and mainly express CD33 but no CD34. Despite previous reports that ATRA-resistant APL cells express more P-gp than ATRA-sensitive ones, P-gp and ATRA-resistance seems to exist independently.

Original languageEnglish
Pages (from-to)739-746
Number of pages8
JournalLeukemia and Lymphoma
Issue number4
Publication statusPublished - Jan 1 2001



  • Acute promyelocytic leukemia (APL)
  • All-trans retinoic acid (ATRA)
  • Multi-drug resistance (MDR)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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