Molecular genetics of acute promyelocytic leukemia

Daniela Diverio, Francesco Lo Coco

Research output: Contribution to journalArticlepeer-review


Characteristic clinical and biological features distinguish acute promyelocytic leukemia (APL) from all other acute myeloid leukemia subsets. A unique genetic lesion, i.e. the PML/RARa fusion gene resulting from the t(15;17) translocation, is present in blast cells of virtually all cases and its detection by PCR allows rapid identification of patients specifically responsive to differentiating treatment with all-trans retinoic acid (ATRA). Research on the biological effect ofPML/RARa has shown that this hybrid protein is able to inhibit differentiation and apoptosis when transfected into a differentiation inducible cell line, and that such block is released upon administration of pharmacological doses of ATRA. The leukemogenic potential of PML/RARa is probably linked to its capacity to form heterodimers with wild-type PML and RARa, thereby interfering with the normal function of such proteins. ATRA has been shown to down-modulate PML/RARa, which in turn would allow greater availability of wild-type PML and RARa, and may account for the therapeutic response to this agent. Recent clinical studies in APL have made extensive use of molecular diagnosis and monitoring by PCR analysis of PML/RARa. These studies have shown that: I) no patient is resistant to the specific differentiating therapy, once the disease is molecularly defined; ii) detection of residual disease during remission is a strong predictor of subsequent relapse and may allow to anticipate treatment. Future reasearch efforts should clarify better the molecular pathogenesis of APL, while an appropriate choice of therapeutic options based on PCR monitoring results may contribute higher cure rates.

Original languageEnglish
Pages (from-to)45-58
Number of pages14
JournalReviews in Clinical and Experimental Hematology
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Hematology


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