METHODS: An 8y/o boy presented with fever, gastrointestinal symptoms, worsening of background asthma and an absolute eosinophil count of ~40,000. Screening for end-organ damage was negative and he was treated empirically for a possible helminth infection. The patient responded well to corticosteroids but eosinophil counts rose upon prednisone taper. Bone-marrow (BM) biopsy was normal except for significantly increased eosinophils. TCR repertoire and screening for associated genetic abnormalities (BCR-ABL1, FIP1L1-PDGFRA, PDGFRB rearrangement) was negative. Despite normal karyotype, cytogenetic studies were performed in search for chromosomal aberrations.
RESULTS: FISH studies using probes to detect AML/ALL associated translocations, revealed a triple signal of the chromosome 21 probe in 20% of BM cells. The probe staining pattern, with close proximity of 2 of the 3 hybridization signals, suggested a partial duplication of chromosome 21. The percent of triple-21-probe cells did not correlate with 50% eosinophils in BM and FISH of skin fibroblasts or peripheral blood. Taken together, these findings support a somatic variation, possibly in a non-eosinophilic cell lineage. Interestingly, the probe used was complementary to RUNX1 (AML1), a transcription factor involved in differentiation of hematopoietic stem cells into myeloid and lymphoid lines.
RUNX1 copy number variance might drive eosinophil proliferation and cytogenetic studies should be considered in the evaluation of HES.