T-lymphoblastic leukemia/lymphoma (also known as T-cell acute lymphoblastic leukemia or “T‑ALL”) is an aggressive cancer caused by an overproduction of immature T cells. T‑ALL most commonly affects children and adolescents, and may involve bone marrow, the thymus, and/or lymph nodes. While the diagnosis of T‑ALL is relatively straightforward in bone marrow, it can be difficult to establish in the thymus since there is no specific immunophenotypic profile to distinguish between T‑ALL cells and normal thymocytes (which are cells that develop in the thymus and are the precursor of T cells) versus thymocytes from epithelial thymic neoplasms (a.k.a., thymomas).
Recent research suggests that the protein LMO2 appears to be a biomarker of transformed T‑precursor cells compared with their normal counterparts. LMO2 (LIM domain only 2) promotes erythroid differentiation through binding genes. Research has found that LMO2 gene translocations have been implicated in the pathogenesis of a small subset of T‑ALLs, and LMO2 has been reported to be expressed in a large proportion of T‑ALLs.
In a recent study published in the American Journal of Clinical Pathology, Mayo Clinic researchers tested the specificity of LMO2 for distinction between neoplastic and non-neoplastic T-precursor cells in the thymus and bone marrow.
“The diagnosis of T-ALL can be difficult because the immunophenotype of neoplastic cells does not differ significantly enough from normal thymocytes,” said Dragan Jevremovic, M.D., Ph.D., a Consultant in Hematopathology at Mayo Clinic, and first author on this paper. “Further, the distinction between normal and neoplastic thymocytes can be difficult even in excisional biopsy specimens and almost impossible in small-needle biopsy specimens.”
Researchers tested 15 patients with thymoma and 30 patients with T‑ALL. The thymocytes in all 15 patients with thymoma as well as the normal thymocytes in the adjacent uninvolved thymuses were negative for LMO2 expression. In contrast, the abnormal T lymphoblasts in all T‑ALL bone marrow clot specimens were uniformly positive for LMO2 expression. The bone marrow core biopsy specimens were also positive for LMO2.
“These findings indicate that LMO2 is expressed in neoplastic lymphoblasts of T‑ALL and is absent in thymocytes of normal thymuses or thymomas,” said Dr. Jevremovic.
LMO2 appears to be a specific marker of transformed T-precursor cells compared with their normal counterparts. However, since thymic epithelial cells express LMO2 weakly and mature B cells express LMO2 strongly, it is important to use T-cell lineage markers to correctly determine LMO2 expression in the target cell population.
“Using T-cell lineage markers is particularly important in small-needle biopsy specimens, in which tissue architecture is not apparent,” said Ellen McPhail, M.D., a Consultant in Hematopathology at Mayo Clinic, and senior author on the paper. “In our study, bone marrows involved by T‑ALL were all positive for LM02. However, decalcification of the bone marrow core biopsy specimen was causing weak staining LMO2 in a few cases, prompting additional staining of bone marrow clot sections, which proved LMO2 positivity.”
The study indicates that LMO2 expression could effectively distinguish normal thymocytes from T‑ALL cells.
“Moving forward, LMO2 may become a standard of care in establishing the diagnosis of T‑ALL,” added Dr. McPhail.