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16-08-2011 | General practice | Article

RUNX1 mutations predict poor outcome in acute lymphoblastic leukemia


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MedWire News: Mutations in the gene encoding runt-related transcription factor 1 (RUNX1) are associated with poor prognosis in patients with T-cell acute lymphoblastic leukemia (T-ALL), study findings indicate.

RUNX1 is essential in the development of all hematopoietic cell lineages, including lymphoid cells, explain Vera Grossmann and colleagues from the Munich Leukemia Laboratory in Germany

Mutations in RUNX1 have previously been described in acute myeloid leukemia (AML), myelodysplastic syndromes, and chronic myelomonocytic leukemia, and are associated with a shorter overall and event-free survival in AML patients.

In addition, recent study findings have suggested that RUNX1 mutations may play a role in lymphatic malignancies.

In the current study, Grossmann and team determined the mutation status of RUNX1 in patients with T-ALL (n=71), B-cell ALL (B-ALL; n=52), or natural killer (NK) cell leukemia (n=5).

Overall, 17 mutations were detected in 15 patients. The mutation rate was highest in T-ALL, with 15 distinct mutations observed in 13 (18.3%) patients. The majority of these patients (n=8) had early T-ALL, while two had cortical T-ALL. Subgroup data was unavailable for the remaining three patients.

Two (3.8%) patients with B-ALL and no patients with NK cell leukemia had RUNX1 mutations.

The researchers observed that, in patients with T-ALL, RUNX1 mutations were associated with a significantly higher mean age (56 vs 42 years for mutation vs no mutation), and a significantly lower white blood cell count (38 vs 82 x 109 cells/l), but not with platelet count, hemoglobin level, gender, or karyotype.

In addition, 2-year survival rates were significantly lower in T-ALL patients with RUNX1 mutations compared with those without mutations, at 44.4% versus 66.6%. This finding was more pronounced among patients with early T-ALL, where the 2-year survival rate was just 28.6% in RUNX1 mutation carriers, compared with 46.0% in patients with the wild-type gene.

"The high incidence of RUNX1 mutations in early T-ALL may indicate an important role in early steps of hematopoietic development," remark Grossmann and co-authors in the journal Haematologica.

They propose that RUNX1 mutation screening is conducted in future clinical studies of T-ALL as this may enable a "more individualized diagnosis and treatment strategy."

By Laura Dean

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