Formin-Like 1 Gene in CLL Overexpressed in Young Patients with Poor Outcome

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[2775] FMNL-1 (Formin-Like 1) Gene in Chronic Lymphocytic Leukemia

(CLL) Is Overexpressed in Young Patients with Adverse Prognostic

Factors and Poor Outcome. Session Type: Poster Session, Board #4-III

Eva Calpe, M.B. Favaro, Marta Crespo, Joao Baptista,

Ana Muntañola, Eva Giné, Sara Saad, Emili Montserrat, Francesc Bosch

Department of Hematology, Laboratory of Experimental Hematology,

Hospital Clinic, IDIBAPS, Barcelona, Spain; Hemocentro da Unicamp,

Cidade Universitaria Zeferino Vaz, Campinas, Brazil

Prognosis of patients with CLL has been traditionally assessed by

using clinical parameters. Although useful, such parameters are a

mere reflection of the biological diversity of CLL.

In this regard, the mutational status of VH genes or ZAP-70

expression separates CLL into two clinical forms with different

presenting features and outcome.

Formins are multidomain proteins characterized by the presence of two

conserved prolin-rich regions, namely formin homology 1 and 2. These

proteins are implicated in a wide range of processes, including

regulation of the cytoskeleton and in the regulation of the signal

for cell survival.

Formin is normally expressed in spleen, lymph node, and bone marrow

cells, and it has been recently found to be overexpressed in T-cell

lymphomas. The aim of this study was to analyze the expression of

FMNL-1 in normal B-cell subsets and in a series of 73 patients

(median age, 59 years; male/female 40/33; Binet A: 90.2%) with CLL.

FMNL-1 expression was analyzed by Western Blot in separate

subpopulations and by quantitative RT-PCR using expression in Jurkat

as baseline. Among normal lymphocytes, FMNL-1 was only expressed in

memory (CD19+CD27+) B-cells and in T-cells.

In CLL cases with a low percentage of T-cells, mean of FMNL-1

expression was 2.18 AU (SD, 1.01 AU). Using an arbitrary cut-off of

3.2 AU, cases with increased expression of FMNL-1 were associated

with a younger age at diagnosis (< 50 yrs), elevated lymphocyte

count, high serum 2-microglobulin (2-m) levels, increased ZAP-70 and

CD38 expression, shorter time to progression, and shorter survival as

compared to cases with low FMNL-1 expression. No relationship was

observed with genetic abnormalities (table).

In summary, among B-cell lymphoproliferative disorders, FMNL-1, a

gene that regulates cell survival, is found only in CLL and its

overexpression correlates with adverse clinical and biological

parameters, particularly in young patients.