Endoglin (CD105) Is Strongly Overexpressed in AML with t(15;17)/PML-RARA and Is Significantly Associated with IDH2 Mutation, but Is Not Expressed in Bone Marrow Endothelial Cells
Zaher Chakhachiro, Zhuang Zuo, Hagop Kantarjian, Jorges Cortes, Khaled AlAyed, Martin Nguyen, Saroj Vadhan-Raj, Jeffrey Medeiros, Carlos Bueso-Ramos. MD Anderson Cancer Center, Houston, TX
Background: Endoglin (CD105) is a tumor-related angiogenesis marker with potential diagnostic and therapeutic implications. CD105 is up-regulated in endothelial cells, is a marker of survival and an imaging target in some human solid tumors, and is a potential antibody-based therapeutic target. The aim of this study was to evaluate the expression of CD105 in the different elements of bone marrow (BM) involved by acute myeloid leukemia (AML).
Design: CD105 expression was assessed in 120 BM specimens involved by AML as well as in 20 negative BM specimens (control group). Immunohistochemistry was carried out by using a monoclonal mouse anti-human CD105 antibody (Dako). CD105 expression was assessed in myeloid and erythroid precursors, megakaryocytes, endothelial cells and stromal cells. Correlation with available molecular and cytogenetic data was performed.
Results: CD105 was diffusely expressed in blasts/promyelocytes of 30 (25%) AML cases. Positive cases included all 9 (100%) AML with t(15;17)(q22;q23)/PML-RARA; 2/2 (100%) AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1; 1/7 (14%) AML with inv(16)(p13.1;q22)/CBFB-MYH11; 1 (100%) AML with t(6;9)(p23;q34)/DEK-NUP214; 5/18 (28%) AML with myelodysplasia-related changes (MRC); 1/3 (33%) therapy-related (t) -AML, and 11/71 (15%) AML not otherwise specified (NOS). The pattern of staining cases of AML with t(15;17)/PML-RARA was strong, homogeneous and cytoplasmic in all cases. Other AML cases showed partial expression in 36 cases and were negative in 54 cases. There was no significant staining in erythroid cells, megakaryocytes, endothelial cells or stromal cells. Control BM specimens showed partial staining for CD105 in 16/20 (80%) cases, mostly in maturing myeloid cells and neutrophils. IDH2 was mutated in 8/20 tested cases with diffuse CD105 expression (4 AML MRC, 3AML NOS, and 1 t-AML). Statistical analysis showed a correlation between diffuse CD105 staining and IDH2 mutation, p=0.002, by 2-sided Chi-square test.
Conclusions: CD105 is overexpressed in a subset of AML, particularly AML with t(15;17)/PML-RARA. Therefore, CD105 is a potential therapeutic target for antibody-based therapy. IDH2 was significantly mutated in 40% of cases diffusely expressing CD105. Interestingly, Endoglin, although a marker of tumor-related angiogenesis, is not overexpressed in endothelial cells in BM specimens involved with AML.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 206, Tuesday Morning