LMO2 (LIM Domain Only 2, Rhombotin-Like 1) Is Expressed in a Subset of Acute Myeloid Leukemia Patients and Correlates with Normal Cytogenetic Status
Jay L Patel, Sarah-Joy Haggstrom, Payam Pournazari, Farid Kosari, Yasodha Natkunam, Adnan Mansoor. University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada; Stanford University School of Medicine, Stanford, CA
Background: LMO2 is a cysteine-rich LIM domain-containing transcription factor that plays an important role in erythropoiesis and is required for definitive hematopoiesis. Expression of LMO2 has been demonstrated in normal germinal center B-cells, B-cell lymphomas, and T lymphoblastic lymphoma/leukemia but has not been studied extensively in acute myeloid leukemia. We studied LMO2 expression in 227 AML patients (median age 64 years, male:female ratio 1.4) with bone marrow morphologic and cytogenetic evaluation.
Design: Triplicate 1mm diameter cores of formalin-fixed paraffin embedded diagnostic bone marrow biopsy tissue were used to create tissue microarrays. Immunohistochemical studies for LMO2 were performed on 4 micron sections according to standard protocol. LMO2 staining on blast cells was scored based on intensity (0,1,2,3) independently by two pathologists and scores >1 were considered positive. Fisher's exact test was performed in order to query for potential correlations between LMO2 expression and AML subtype as well as cytogenetic data.
Results: LMO2 was expressed in 38% of cases (n=86/227). LMO2 expression is more common in patients with normal karyotype vs. abnormal karyotype (62% vs. 33%, p<0.0001). There was no statistically significant correlation between LMO2 positivity and specific cytogenetic abnormalities including t(8;21)(q22;q22) and inv(16)(p13;q22) or t(16;16)(p13;q22) vs. those with normal karyotype/FISH studies (50% vs. 62%, p=0.15; 20% vs. 62%, p=0.005, respectively). Further, no correlation between LMO2 expression and AML with myelodysplasia-related changes vs. other AML subtypes was observed (33% vs. 71%, p=0.07). Among AML patients with various FAB subtypes, those with monocytic morphology (M4 or M5 by FAB criteria) appear less likely to express LMO2 than other AML subtypes (43% vs. 84%, p=0.05). There was no statistically significant association between LMO2 expression and overall survival (p=0.37).
Conclusions: LMO2 is expressed in a subset of AML patients and is associated with normal karyotype. The precise mechanism of LMO2 expression in these patients is unknown at this time. The lack of karyotypic abnormalities in most of these cases suggests that the mechanism differs from that of LMO2 activation in T lymphoblastic lymphoma/leukemia in which translocations involving LMO2 at 11p13 mediate protein expression.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 204, Tuesday Morning