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Rare Acute Leukemia Variants Involving Retinoic Acid Receptor Genes

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Acute Promyelocytic Leukemia

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Abstract

Acute promyelocytic leukemia (APL) is typically characterized by the balanced reciprocal translocation t(15;17)(q24.1;q21.2) which fuses the promyelocytic leukemia (PML) and retinoic acid receptor-α (RARA) gene. PML-RARA oncoprotein is the key pathogenetic player in APL pathogenesis and acts through the transcriptional repression on multiple RARA target genes, causing the inhibition of cellular differentiation and uncontrolled proliferation of undifferentiated elements [1]. Rarely, patients presenting with clinical and morphological features suggestive of APL lack either cytogenetic evidence of t(15;17) or molecular evidence of PML-RARA and are subsequently recognized to harbor instead variant translocations involving RARA gene fused to partner genes other than PML To date, at least 12 variant translocations involving RARA have been identified, including ZBTB16/RARA (formerly named PLZF-RARA) [6], NPM-RARA, NuMA-RARA, STAT5B/RARA, PRKAR1A/RARA, BCOR/RARA, FIP1L1/RARA, OBFC2A/RARA, GTF2I/RARA , and the most recent IRF2BP2/RARA and FNDC3B/RARA . Opposite to PML-RARA-positive APL, these variant translocations display in the majority of cases low or none sensitivity to specific target agents as arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA). We will discuss in details the clinico-biologic characteristics of the different variant translocations reported up to date

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Authors and Affiliations

  1. Department of Biomedicine and Prevention, University Tor Vergata, via Montpellier 1, Rome, Italy

    Laura Cicconi M.D.

  2. Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada

    Oussama Abla M.D.

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  1. Laura Cicconi M.D.
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Correspondence to Laura Cicconi M.D. .

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Editors and Affiliations

  1. Division of Hematology/Oncology, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

    Oussama Abla

  2. Department of Hematology, University of Tor Vergata, Rome, Italy

    Francesco Lo Coco

  3. Department of Medicine, Hospital Universitari i Politecnic La Fe, University of Valencia, Valencia, Spain

    Miguel A. Sanz

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Cicconi, L., Abla, O. (2018). Rare Acute Leukemia Variants Involving Retinoic Acid Receptor Genes. In: Abla, O., Lo Coco, F., Sanz, M. (eds) Acute Promyelocytic Leukemia . Springer, Cham. https://doi.org/10.1007/978-3-319-64257-4_20

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