t(15;17)(q22;q21), t(15;17)(q22;q12), or t(15;17)(q24;q21)? A diagnostic entity in search of unanimity.

The balanced reciprocal translocation, t(15;17), of acute promyelocytic leukemia (APL) was first reported in 1977 [1], and the breakpoints were assigned in 1984 to 15q22 and 17q21 [2]. This notation subsequently became the consensus of the Fourth International Workshop on Chromosomes in Leukemia (FIWCL-1984) [3]. The Human Gene Mapping 9 Committee (HGM9C-1987) assigned the breakpoints to bands 15q22 and 17q11–12 [4]. The breakpoint on chromosome 17 was later found in 1990 to be located in the retinoic acid receptor gene a (RARA) [5], and, in less than a year, was sequenced and specifically localized to 17q21 [6]. However, events that followed FIWCL-1984 turned out to be more challenging with regard to the chromosome 15 breakpoint. Six years after FIWCL1984, de The et al. [7] reported that the breakpoint on chromosome 15 was in fact localized to the q23–q24 bands [they named this locus myl (for ‘‘myelocytic leukemia’’)]. Unfortunately, they did not fully report their results in the paper, which led to the findings being dismissed by much of academia. However, the same 15q23–24 conclusion was soon obtained in 1991 by in situ hybridization [8], and myl was renamed PML (for ‘‘promyelocytes’’). This result was soon challenged by Kakizuka et al. [9], who reported in the same year that the breakpoint was localized to 15q22, and not 15q23–24. Subsequently, the advisory committee of the World Health Organization (WHO) Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues meeting in 1997 [10] recommended the term ‘‘acute promyelocytic leukemia [AML with t(15;17) (q22;q11–12) and variants, PML/RAR-alpha],’’ a reiteration of the HGM9C-1987, thereby rejecting the FIWCL-1984 and de The (1990) designations. Donti et al. [11] argued in 1991 that ‘‘If the 17q12 band remains on the APL 17q-marker, the G-negative chromosomal material below this band is a portion of 17q21 and not 15q22. What was interpreted as band 17q12 on the reciprocal 15q ? chromosome would be the 15q23 band, and, in consequence, the chromosome 15 breakpoint would be located on 15q24 and not on the 15q22 band.’’ The study by Stock et al. [12], using a combination of G-banding, fluorescence in situ hybridization, and chromosome microdissection/reverse in situ hybridization, leaves no doubt that the breakpoints are 15q24 and 17q21.1. Stock et al. [12] believe that the main reason for the inconsistency of results is related to the considerable inaccuracy of the international system for cytogenetic nomenclature ideogram for chromosome 15 at the 400and 850-band levels. Unfortunately, the WHO-2008 Classification of Tumours of the Haematopoietic and Lymphoid Tissues continues to recommend ‘‘acute promyelocytic leukemia (AML with t(15;17)(q22;q12); PML/RARA).’’ A search of PubMed using the keyword t(15;17)(q22;q21), the incorrect FIWCL-1984 notation, yields 80 references. Changing the keyword to t(15;17)(q22;q12), currently recommended by WHO-2008, provides 39 references, while the correct notations t(15;17)(q24;q21) or t(15;17)(q24;q21.1) yield only 6 references, the most recent one of which dates back to 2001. Have we (ourselves included) settled into such a passive, ‘‘no critical questioning allowed,’’ state of mind that when we encounter an actual case of karyo typically defined t(15;17)(q24;q21) APL, with breakpoints inconsistent with A. Rashidi (&) Department of Internal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 410, Norfolk, VA 23507, USA e-mail: rashida@evms.edu