Cytoplasmic Location Of Shuttling Protein Often Seen With AML

NEW YORK (Reuters Health) - Nucleophosmin (NPM), a shuttling protein that regulates a p53 tumor-suppressor pathway, is normally most abundant in nucleoli. Now, new research indicates that a large group of patients with acute myelogenous leukemia (AML) have NPM that accumulates instead in the cytoplasm.

This abnormal subcellular location appears to result from NPM gene mutations and is associated with a normal karyotype and responsiveness to induction chemotherapy, according to a report in The New England Journal of Medicine for January 20th.

The findings are based on an analysis of bone marrow-biopsy specimens obtained from 591 patients with primary AML. For comparison, the location of NPM in 135 secondary AML specimens and in 980 non-AML neoplasms was also determined.

Dr. Brunangelo Falini, from the University of Perugia, Italy, and colleagues found that 208 (35.2%) of the primary AML specimens showed cytoplasmic NPM, a finding not observed in any of the comparison specimens.

Compared with AML specimens showing nucleolar NPM, those with cytoplasmic NPM had a high rate of FLT3 internal tandem duplications and an absence of CD34 and CD133, the investigators note. Cytoplasmic localization was not associated with recurrent genetic abnormalities.

"Our findings are important because no chromosomal rearrangement is visible by standard karyotyping in 40% to 50% of cases of AML, and uncertainty clouds some of the biologic and clinical features in these patients," the authors state.

In a related editorial, Dr. Silvia Grisendi and Dr. Pier Paolo Pandolfi, from Memorial Sloan-Kettering Cancer Center in New York, comment that "whatever its role in leukemogenesis may turn out to be, the identification of cytoplasmic NPM in a high proportion of cases of AML is an important finding, not only because it has clinical implications but also because it calls for further studies of the molecular basis of the role of NPM in oncogenesis."

Source: N Engl J Med 2005;352:254-266,291-292. [ Google search on this article ]

MeSH Headings: Cytoplasm : DNA-Binding Proteins : Leukemia, Myelocytic, Acute : Nuclear Proteins : Phosphoproteins : Leukemia, Nonlymphocytic, Acute : Genes, p53 : Protein p53