Molecular and clinical studies of severe congenital neutropenia or Kostmann disease

Our research interests also include cancer research with focus on apoptosis signaling in malignant and non-malignant (pre-malignant) hematological diseases, such as severe congenital neutropenia (SCN) or Kostmann disease, and hematopoietic malignancies such as leukemia, lymphoma, and myeloma (principal funding: Swedish Cancer Research Foundation and Stockholm County Council (ALF Project). We actively collaborate with clinical colleagues at the Karolinska University Hospital and with several other national and international researchers in Europe and the United States.

In particular, we have contributed to the identification of mutations in the gene encoding HS-1-associated protein X-1 (HAX-1) in patients with autosomal recessive forms of Kostmann disease, a condition that was first described by the Swedish pediatrician, Dr. Rolf Kostmann, in the 1950s. We have shown that myeloid precursors from these patients undergo accelerated, mitochondria-dependent apoptosis. More recent studies are beginning to unravel a prominent role for HAX-1 in apoptosis signaling not only in the hematopoietic compartment, but also in the central nervous system. Moreover, several different cellular and viral binding partners of HAX-1 have been identified thus pointing toward a complex and multifunctional role of this protein (Fadeel & Grzybowska, Biochem Biophys Acta, 2009). We recently reported that HAX-1 is overexpressed in certain forms of B lymphoma and we are now aiming to delineate the role of HAX-1 in hematopoietic malignancies.

Our research also aims to identify novel gene defects in SCN patients of unknown genetic etiology. The latter studies are performed in part in collaboration with the Science for Life Laboratory.



Bengt Fadeel

Phone: +46-(0)8-524 877 37
Organizational unit: Molecular Toxicology