FOXP1 and BCL2 Show Similar Immunoenzymatic Pattern in Bone Marrow Trephines of Chronic Lymphocytic Leukemia Patients

Abstract

Indolent B lymphoproliferative disorder, chronic lymphocytic leukemia (CLL) represents one of the most common hematologic diseases in the Western world. Although there are many disease development markers known so far, for example, B-cell lymphoma/leukemia (BCL) 2, new ones are needed for better understanding course of the disease. FOXP1 is known to be strongly expressed after B-cell activation. Its essential role in B-cell development suggested that it could also have a role in a various tumor B-cells. We have analyzed 74 bone marrow samples from B-CLL patients for presence of FOXP1 and its gene aberrations in tumor cells. Our results showed presence of FOXP1 protein mostly in the same tumor cells as BCL2 protein, and their specific immunostaining pattern. Diffuse immunostaining pattern of both proteins is present in patients with higher clinical stages of B-CLL and with some other markers that indicate worse outcome of the disease. Thus, FOXP1 and/or BCL2 immunostaining of bone marrow trephine sections could serve as an immunohistochemical marker in B-CLL.

CRISPR/Cas9-Mediated Foxp1 Silencing Restores Immune Surveillance in an Immunocompetent A20 Lymphoma Model

“…This model thus provides a system in which to study the interplay between a B-cell lymphoma and its immune microenvironment. Importantly, FOXP1 is a marker of adverse outcome in other B-cell malignancies, including marginal zone lymphoma (25), chronic lymphocytic leukemia (26), and follicular lymphoma (27,28), Foxp1 expression patterns (both full length protein and smaller isoforms) and its repression of MHC-II, previously observed in human ABC-DLBCL (9), are both conserved in the murine A20 model. The current study also demonstrates that transient Foxp1 silencing in the A20 cell line did not compromise cell viability.…”

Cellular origin and pathophysiology of chronic lymphocytic leukemia

“…The derivation of CLL from CD5 + B cells has major implications for our understanding of its pathogenesis. First, CLL often express polyreactive and autoreactive BCR specificities Chu et al, 2008;Chu et al, 2010), and it is an important question whether this holds true for normal mature CD5 + B cells as well. Initial studies suggest that CD5 + B cells may possibly be reactive only to selected autoantigens (Hervé et al, 2005).…”

“…FOXP1, a transcription factor involved in lymphocyte development and with a potential role of an oncogene in lymphomas (Koon et al, 2007), is increased in CLL in comparison with conventional B cells (Korać et al, 2009). Similarly, the transcription factor LEF1, which has important functions in lymphopoiesis, promotes CLL survival and is not expressed in conventional mature B cells (Gutierrez et al, 2010;Tandon et al, 2011).…”

Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL

“…BCL2 protein overexpression has been reported to occur in 24-66 % of cases of DLBCL [26,27]. It has been postulated that in DLBCL changes in FOXP1 and BCL2 were interdependent and that the presence of an additional copy of FOXP1 gene will cause BCL2 protein to be active [28,29]. The role of miR-34a as a tumor suppressor may be more directly related to p53 and BCL2.…”