Unknown

Rare disease with unknown incidence

A 64-year-old male presented with fatigue and weight loss for three months. Physical examination found a enlarged spleen (6 cm below the left costal margin) but was negative for adenopathy, bruise/bleed and hepatomegaly. Peripheral blood counts demonstrated leukocytosis and thrombocytopenia with white blood cells (WBC) 128·68 × 109/l, haemoglobin (HGB) 137 g/l and platelet count 36 × 109/l. A differential count found 35·6% neutrophils, 14·2% lymphocytes, 13·3% monocytes, 3% basophils, 1% myelocytes and 32·6% eosinophils (absolute eosinophil count 43 × 109/l).

Bone marrow aspiration smears showed marked granulocytic proliferation, with a myeloid-to-erythroid ratio of 34.8:1. Myeloblasts and promyelocytes were not increased. Eosinophils were significantly increased, accounting for 31% of all nucleated cells, with some of them showing sparse granulation and cytoplasmic vacuolation. Erythroid and lymphoid elements were markedly proportionally decreased with no significant dysplasia.

Fig. 1: Eosinophilia with cytoplasmic vacuolation

The expected fusion protein contains an intact BTB/POZ domain and the FLT3 tyrosine kinase domain (TKD). The ZBTB44-FLT3 fusion protein is likely constitutively activated by ZBTB4 BTB/POZ-induced erization and cross-phosphorylation by the FLT3 tyrosine kinase.

Fig. 5   Functional motifs of ZBTB44, FLT3 and ZBTB44-FLT3 fusion. BTB: broad-complex, tramtrack and bric a brac, also known as the POZ domain; ZF, zinc fingers; IG-like, immunoglobulin-like loops; TM, transmembrane domain; TK, tyrosine kinase domain.