Faculty Bibliography

BACKGROUND: Mycosis fungoides (MF) is often associated with eosinophilia and portends a poorer prognosis. MF is more common in blacks and follows a more aggressive course compared with whites. OBJECTIVE: We further elucidate racial differences between blacks and whites with MF, focusing on blood eosinophilia. METHODS: The records of 345 patients with MF were reviewed for demographic, clinical, and pathologic data and evaluated by analysis of variance. RESULTS: The average age at diagnosis for blacks was 45 years and was 55 years for white patients (P < .001). In the cohorts of patients with and without blood eosinophilia, the average maximum blood eosinophil count had a greater range in blacks. Independent of race, blood eosinophilia was predictive of more advanced disease (P < .0001), increased number of treatment types (P < .002), and less responsiveness to treatment (P < .0006). LIMITATIONS: This was a retrospective study at a single institution. CONCLUSIONS: These differences observed in eosinophil values may highlight disparities in MF diagnosis or a difference in pathophysiology between races.

BACKGROUND: Hematolymphoid neoplasms frequently harbor recurrent genetic abnormalities. Some of the most well recognized lesions are chromosomal translocations, and many of these are known to play pivotal roles in pathogenesis. In lymphoid malignancies, some translocations result from erroneous V(D)J-type events. However, other translocation junctions appear randomly positioned and their underlying mechanisms are not understood. RESULTS: We tested the hypothesis that genomic repeats, including both simple tandem and interspersed repeats, are involved in chromosomal translocations arising in hematopoietic malignancies. Using a database of translocation junctions and RepeatMasker annotations of the reference genome assembly, we measured the proximity of translocation sites to their nearest repeat. We examined 1,174 translocation breakpoints from 10 classifications of hematolymphoid neoplasms. We measured significance using Student's t-test, and we determined a false discovery rate using a random permutation statistics technique. CONCLUSIONS: Most translocations showed no propensity to involve genomic repeats. However, translocation junctions at the transcription factor 3 (TCF3)/E2A immunoglobulin enhancer binding factors E12/E47 (E2A) locus clustered within, or in proximity to, transposable element sequences. Nearly half of reported TCF3 translocations involve a MER20 DNA transposon. Based on this observation, we propose this sequence is important for the oncogenesis of TCF3-PBX1 acute lymphoblastic leukemia.