Acute megakaryoblastic leukemia (M7 AML) and T lymphoblastic leukemia

Only two cases to date: a 5-year-old female patient (Tosi et al, 2005) and a 26-year-old male patient (Romana et al, 2006).

FISH technique with the NUP98 probe and BAC RP11-900M13 probe has been used to confirm the translocation in the reported case (Romana et al, 2006).

The T-ALL adult patient showed an additional abnormality of 12p13 (Romana et al, 2006).

NUP98/CCDC28A

Nucleotide sequence analyses revealed an in-frame fusion between the 13th exon of NUP98 and the second exon of CCDC28A. A reciprocal CCDC28A/NUP98 fusion transcript was detected but is likely devoid of biological activity due to the lack of a predicted fusion protein (Petit et al, 2012).

NUP98/CCDC28A

In mouse models it has been demonstrated that the enforced NUP98/CCDC28A expression promoted the proliferative and self-renewal capacities of hematopoietic progenitors and rapidly caused fatal myeloproliferative neoplasms and defects in the differentiaton of the erythro-megakaryocytic lineage. Although the leukemogenic mechanism remains unknown, NUP98/CCDC28A retains the NUP98 GLFG-repeats able to associate with core binding protein and/or EP300 and has a nuclear localization suggesting possible transactivation activity. The transformation mediated by NUP98/CCDC28A was not associated with deregulation of the HOXA-Meis1 pathway, a feature shared by a diverse set of NUP98 fusions. Additional investigation will be needed to elucidate the role of NUP98/CCDC28A in lymphoid transformation (Petit et al, 2012).

NUP98/CCDC28A