A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease.

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BlankA novel adoptive transfer model of chronic lymphocytic leukemia suggests a

key role for T lymphocytes in the disease.

D Bagnara, MS Kaufman, C Calissano, S Marsilio, P Patten, R Simone, P Chum, XJ

Yan, SL , JE Kolitz, S Baskar, C Rader, H Mellstedt, H Rabbani, A Lee, PK

Gregersen, KR Rai, and N Chiorazzi

Blood, March 8, 2011;

A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key

role for T lymphocytes in the disease.

Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown

etiology. Understanding the biology of CLL cells, particularly cell maturation

and growth in vivo, has been impeded by the lack of a reproducible adoptive

transfer model. We report a simple, reproducible system in which primary CLL

cells proliferate in NOD/SCID/?c(null) mice under the influence of activated

CLL-derived T lymphocytes. By co-transferring autologous T lymphocytes,

activated in vivo by alloantigens, the survival and growth of primary

carboxyfluorescein succinimidyl ester-labeled CLL cells in vivo is achieved and

quantified. Using this approach, we have identified key roles for CD4(+) T cells

in CLL expansion, a direct link between CD38 expression by leukemic B cells and

their activation, and support for CLL cells preferentially proliferating in

secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL

cells in vivo, deciphering involvement of non-leukemic elements and non-genetic

factors promoting CLL cell growth, identifying and characterizing potential

leukemic stem cells, and permitting pre-clinical studies of novel therapeutics.

Because autologous activated T lymphocytes are two-edged swords, generating

unwanted graph-versus-host and possibly autologous anti-tumor reactions, the

model may also facilitate analyses of T-cell populations involved in immune

surveillance relevant to hematopoietic transplantation and tumor cytoxicity.

PMID: 21385850