Do RARA/PML fusion gene deletions confer resistance to ATRA-based therapy in patients with acute promyelocytic leukemia?

Atypical mRNA fusions in PML‐RARA positive, RARA‐PML negative acute promyelocytic leukemia

“…Although some authors have linked these deletions with an adverse prognosis, case numbers were low and clinical follow-up data were not available for all patients. The presence of deletions of RARA and/or PML identified by FISH analysis in two APL patients was recently linked to potential resistance to ATRA-based therapy (Subramaniyam et al, 2006). In the first patient in this study, a deletion of $800 kb encompassed a major part of the 3 0 end of PML and the entire 5 0 end of RARA on der(17)t(15;17) including Exons 1 and 2.…”

“…Structural alterations including duplications, deletions, and amplification of ETV6 or RUNX1 were reported as favorable prognostic factors in ETV6-RUNX1 positive childhood acute lymphoblastic leukemias (Martinez-Ramirez et al, 2001). Standard G-banding (resolution: $5-10 Mb), FISH (resolution: $100 kb), and array-based comparative genomic hybridization (resolution: $5-10 kb) (aCGH) identified submicroscopic deletions on the der(15) or der(17) in only a very small number of APL patients with t(15;17) (5/198; 3%) (Lafage-Pochitaloff et al, 1995;Kolomietz et al, 2001;Specchia et al, 2002;Bacher et al, 2005;Subramaniyam et al, 2006;Moon et al, 2007;Dolan et al, 2008). Although some authors have linked these deletions with an adverse prognosis, case numbers were low and clinical follow-up data were not available for all patients.…”

Acute Myelogenous Leukemia without Maturation with a Retinoic Alpha-Receptor Deletion: A Case Report

“…Very rare examples of non-APL with this translocation have been identified [9]. Additionally, a small number of APL with complex chromosomal rearrangements involving deletions at the RARα /17q locus have been described [4, 5, 6, 7, 8]. To our knowledge, RARα /17q locus deletions have not previously been detected in AML without differentiation (AML-M1).…”

“…Occasional APL cases carry complex genomic rearrangements which include RARα sequence deletions. These deletions are apparently very rare compared to similar deletions in other leukemias associated with disease-specific cytogenetic changes [4, 5, 6, 7, 8]. Additionally, t(15;17)(q22;q21) is rare in non-APL acute myeloid leukemias (AMLs), with only rare examples of this translocation identified in AML without maturation and AML with maturation (FAB M1 and M2 subtypes, respectively) [9].…”

Acute Promyelocytic Leukemia: A Model Disease for Targeted Cancer Therapy

“…Not much is known about the role of this protein in the pathogenesis of APL. However, one study has described a possible link between RARA/PML fusion gene deletions and resistance to ATRA-based therapy (Subramaniyam et al, 2006).…”