Fig. 1.

GATA-2 mutations in myeloid blast transformation of CML. (A) DNA sequencing analyses detect a recurrent T/G heterozygosity at 1,075 nt (coding region sequence) of GATA-2 exon 5 in both cDNA and genomic DNA samples isolated from BM cells of CML patients during AP/BC. (B) An 18-bp deletion of the GATA-2 gene from nucleotide 1021 to nucleotide 1038 specifically detected at BC phase in a BM sample of patient UPN6. (C) MALDI-TOF MS confirms a GATA-2 T-to-G mutation within BM cells at BC phase. (D) The detection of the nucleotide 1075 T-to-G mutation in BM samples of three patients by allele-specific PCR at AP/BC but not at CP. (E) The GATA-2 gene deletion results in a deletion of amino acids 341–346 (Δ341–346) around the ZF1 domain border. L359V substitution is within ZF2 domain. (F) Morphological and histochemical examinations of BM samples from patient UPN3 with L359V or from patient UPN6 with Δ341–346. (a) Wright's staining of a BM cellular smear from patient UPN3 at CP. (b–g) Examination on the BM samples from UPN3 at BC. (b) Wright's staining. (c) Myeloperoxidase staining, a specific marker of myeloid cells. Note the presence of strong positive, weak positive, or even negative contingents, suggesting the identities of myeloblasts and monoblasts. (d) Periodic acid Schiff staining. (e) Naphthol AS-chloracetate esterase staining, a marker of granulocytes. (f) Naphthol AS-D acetate esterase (NAS-DAE) staining. (g) Inhibition of NAS-DAE staining by sodium fluoride, a test to distinguish granulocytes from monocytes. (h) Wright's staining of BM samples from UPN 6 at BC shows the presence of eosinophilia. (G) Disease progression of CML patients with GATA-2 mutation compared with those without GATA-2 mutation.