Differences in gene expression profiles in blood versus lymph nodes and bone marrow from patients with Chronic Lymphocytic Leukemia.

Chronic Lymphocytic Leukemia is the most common adult leukemia in the Western
world. Until now there is no curative therapy; only complete remission for a
short period can be accomplished. There is no explanation for the resistance to
therapy at this moment. Our hypothesis is that the leukemic white blood cells
are sensitive for therapy, but the leukemic cells in the bone marrow and lymph
nodes are therapy resistant. In many types of cancer there is an error in the
programmed cell death, a process also known as apoptosis. This process is
regulated by pro- apoptotic and anti- apoptotic proteins. One important pro-
apoptotic protein is Noxa. Previously, we have shown that in a multiplex PCR
(MLPA) in lymph nodes of CLL patients there is lower expression of Noxa
compared to leukemic cells in peripheral blood. We suggest this could be an
explanation for therapy resistance (in the lymph nodes). By MLPA we
investigated 35 different genes that are important in apoptosis, but there are
many other genes that play an important role in CLL. In our current study, we
want to generate gene expression profiles, by c-DNA micro array, to identify
the differences between the leukemic cells in the lymph nodes and bone marrow
versus peripheral blood. Thus, we hope to identify the genes that are important
in the resistance for therapy.

To identify the differences in gene expression profiles of leukemic cells in
lymph nodes and bone marrow versus peripheral blood in patients with chronic
lymphocytic leukemia. Thereby investigating which differences are important in
the resistance for therapy and, potentially, in the development of novel
therapeutic regimes.

In this study CLL patients are eligible who are planned for a diagnostic lymph
node extirpation or bone marrow biopsy. During the bone marrow biopsy some
extra bone marrow fluid will be aspirated and during the lymph node extirpation
some extra tissue will obtained. On the same day a blood withdrawal of 35 ml
will be performed. Patients do not qualify for compensation.

The lymph node extirpation and bone marrow biopsy are planned for a diagnostic
purpose. During the bone marrow biopsy 5 ml extra bone marrow fluid will be
aspirated and during the lymph node extirpation some extra tissue will be
removed. This will not prolong the intervention. On the same day there will be
a blood withdrawal. This can cause some inconvenience and a small haematoma.
The objective of the study is to identify the differences in gene expression in
lymph node and bone marrow versus peripheral blood and thereby investigate
which differences are important in the resistance for therapy and develop a new
targeted therapy. Thus, there will be no direct benefit for the individual
patients; however we hope that other (future) patients will benefit from the
knowledge obtained in the current study.