Translocation t(11;17) Is Not Always Associated with Acute Myeloid or Acute Promyelocytic Leukemia

Abstract 5044

Translocation t(11;17) is a rare chromosomal aberration that as an isolated entity is not pathognomonic of any hematologic disorder. Within the wide spectrum of chromosomal translocations, it is well recognized, though is uncommon, as a variant of acute promyelocytic leukemia (APL), with specific break-point at the PLZF gene on chromosome 11 forming a fusion gene the PLZF/RAR-α almost invariably resistant to all-trans retinoic acid (ATRA). Abnormal fusion of 11q23 mixed-lineage-leukemia (MLL) gene with the SEPT9 transcript on chromosome 17q25 in an acute monocytic (M5b) variant of acute myeloid leukemia (AML) is another example of an acute leukemia characterized by this chromosomal aberration. Sporadically, it has also been reported as a transient chromosomal break-point (q14;q12) in chronic myeloid leukemia (CML) (Olazábal et al. Cancer Genet Cytogenet. 2008). However, this chromosomal translocation is not well recognized in myelodysplastic syndrome (MDS) though nearly 50% of de novo and 80% of therapy-induced MDS (t-MDS) harbor karyotypic anomalies. In the present study, we report the natural history, clinical characteristics, outcome and the breakpoint regions in 2 patients with MDS and t(11;17) treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 2000–2011. The first patient is an asymptomatic 28-year-old man presenting with a platelet count of 72,000/μL. The bone marrow morphology was consistent with a MDS, and clonal abnormality with karyotype 46, XY, t(11;17)(p11.2;p13) as a sole abnormality. Molecular analysis was negative for PML/RAR-α RNA transcript. The second patient is a 59-year-old woman who presented with mild fatigue, hemoglobin of 10.6 g/dL, platelet count of 84,000μ/L and was diagnosed with del(5q) MDS. Her bone marrow morphology was consistent with refractory cytopenia with multilineage dysplasia (RCMD) as defined by the World Health Organization (WHO),with an international prognostic scoring system (IPSS) intermediate-1 risk (score of 0.5). Her karyotype showed the translocation t(11;17) as a part of a clonal abnormality with karyotype 46,XX,del(5)(q13q33),t(11;17)(q24;q23). Both patients are being followed without treatment, as the peripheral blood counts are stable. The second patient is being considered for an allogeneic hematopoietic stem cell transplant (HSCT).

These 2 patients are examples of non-APL/MLL-AML related translocation t(11;17) with different break-point regions. To our knowledge, there have only been several isolated cases of this translocation in patients with MDS. In this group of reported cases that included 4 women and 2 men (out of which 3 were children), the median age at presentation was 35; 2 cases were primary MDS while other 4 represented either t-MDS, MDS-derived AML, primary acute lymphoblastic leukemia (ALL) or AML. One of the previously reported patients with t(11;17)-related MDS was treated with a single course of decitabine, then subsequently underwent an unrelated-donor HSCT with an assumed favorable long-term outcome (Kreuziger et al. Leuk Res. 2007). Alternatively, the response to treatment in those of AML-M5b subtype and PLZF/RAR-α t(11;17)(q23;q11.12) was very poor (Tetsuya et al. Int J Hematol. 2008; Guidez et al. Leukemia. 1994).

Thus, although the course of our 2 MDS patients associated with t(11;17) has been indolent to date, a larger cohort of patients and a longer follow-up is necessary before conclusions regarding prognosis and outcome can be made for this subgroup of patients with MDS. A review of the literature suggests these currently reported patients are the first with these particular break-point variations, and among the first altogether of adults with non-therapy related MDS with translocation t(11;17).