Low LIM-domain only 2 (LMO2) expression in aggressive B cell lymphoma correlates with MYC and MYC/BCL2 rearrangements, especially in germinal center cell-type tumors

Chapman, Jennifer R.; Verdún, Ramiro E.

doi:10.1080/10428194.2021.1927020

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…In cases classified by the Hans algorithm, LMO2 expression has been shown to correlate with the genetic features of DLBCL. In that study, LMO2 was considered positive if more than 30% of lymphoma cells showed nuclear positivity; MYC was considered positive if more than 40% of lymphoma cells showed nuclear positivity [243]. The GCB cases of DLBCL with negative or low (<30%) expression of LMO2 were significantly enriched in the subtype with dual MYC and BCL2 gene rearrangements [243].…”

Section: Immunophenotypic Features Characteristic Of Mature B-cell Ly...mentioning

confidence: 98%

“…In that study, LMO2 was considered positive if more than 30% of lymphoma cells showed nuclear positivity; MYC was considered positive if more than 40% of lymphoma cells showed nuclear positivity [243]. The GCB cases of DLBCL with negative or low (<30%) expression of LMO2 were significantly enriched in the subtype with dual MYC and BCL2 gene rearrangements [243]. High (>30%) LMO2 expression was associated with isolated BCL2 translocations; it was suggested that LMO2 expression might be downregulated or lost after MYC rearrangements in aggressive cases of DLBCL.…”

Section: Immunophenotypic Features Characteristic Of Mature B-cell Ly...mentioning

confidence: 99%

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Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 3: Mature Leukemias/Lymphomas

Kansal

2023

Lymphatics

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The diagnosis and treatment of lymphoid neoplasms have undergone a continuously progressive positive change in the last three decades, with accelerated progress in the previous decade due to the advent of genomics in cancer diagnosis. Significantly, there has been an increasing emphasis on integrating molecular genetics with clinical, morphologic, immunophenotypic, and cytogenetic evaluation for diagnosis. As we think of moving forward with further advances in the genomics era, it is first helpful to understand our current state of knowledge and how we achieved it in the challenging and complex field of lymphoid neoplasms, which comprise very heterogeneous neoplastic diseases in children and adults, including clinically acute lymphoblastic leukemias (ALLs) arising from precursor lymphoid cells and clinically indolent and aggressive lymphomas arising from mature lymphoid cells. This work aims to provide an overview of the historical evolution and the current state of knowledge to anyone interested in the field of lymphoid neoplasms, including students, physicians, and researchers. Therefore, I discuss this complex topic in three review manuscripts, designated Parts 1–3. In Part 1, I explain the basis of the diagnostic classification of lymphoid neoplasms and its evolution up to the current fifth edition of the World Health Organization classification of hematolymphoid neoplasms, and the crucial importance of diagnostic tumor classifications in achieving and advancing patient care and precision medicine. In the second and third manuscripts, I discuss current diagnostic considerations for B-ALL and T-ALL (Part 2) and common indolent and aggressive mature leukemias/lymphomas (Part 3), including significant updates in the WHO 2022 classification, newly described entities, and concepts, including genetic predisposition to ALLs and lymphomas, and throughout emphasizing the essential integration of molecular genetics with clinical, morphologic (pathologic), immunophenotypic, and cytogenetic evaluation, as is required for precise diagnosis of the type of lymphoma/leukemia in any patient.

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Section: Immunophenotypic Features Characteristic Of Mature B-cell Ly...mentioning

confidence: 98%

Section: Immunophenotypic Features Characteristic Of Mature B-cell Ly...mentioning

confidence: 99%

Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 3: Mature Leukemias/Lymphomas

Kansal

2023

Lymphatics

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Round-robin testing for LMO2 and MYC as immunohistochemical markers to screen MYC rearrangements in aggressive large B-cell lymphoma

et al. 2023

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Aggressive large B-cell lymphomas (aLBCL) include a heterogeneous group of lymphomas with diverse biological features. One of the approaches to the diagnosis of aLBCL is based on the identification of MYC rearrangements (MYC-R), in addition to BCL2 and BCL6 rearrangements by genetic techniques, mainly fluorescent in situ hybridization (FISH). Because of the low incidence of MYC-R, the identification of useful immunohistochemistry markers to select cases for MYC FISH testing may be useful in daily practice. In a previous work, we identified a strong association between the profile CD10 positive/LMO2 negative expression and the presence of MYC-R in aLBCL and obtained good intralaboratory reproducibility. In this study, we wanted to evaluate external reproducibility. To evaluate whether LMO2 can be a reproducible marker between observers 50 aLBCL cases were circulated among 7 hematopathologists of 5 hospitals. Fleiss’ kappa index for LMO2 and MYC were 0.87 and 0.70, respectively, indicating high agreement between observers. In addition, during 2021–2022, the enrolled centers included LMO2 in their diagnostic panels to evaluate prospectively the utility of the marker, and 213 cases were analyzed. Comparing LMO2 with MYC, the group of CD10 positive cases showed higher specificity (86% vs 79%), positive predictive value (66% vs 58%), likelihood positive value (5.47 vs 3.78), and accuracy (83% vs 79%), whereas the negative predictive values remained similar (90% vs 91%). These findings place LMO2 as a useful and reproducible marker to screen MYC-R in aLBCL.

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Chromogenic LMO2 mRNA ISH Expression Correlates with LMO2 Protein and Gene Expression and Captures Their Survival Impact in Diffuse Large B-Cell Lymphoma, NOS

Papaleo,

Molina-Alvarez,

Onieva

et al. 2024

Cancers

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Background: LMO2 is a relevant gene involved in B-cell ontogeny and a survival predictor of aggressive large B-cell lymphomas (aLBCL). Most studies assessing LMO2 mRNA expression have relied on microarray platforms or qRT-PCR methods, overlooking tissue morphology. In this study, we evaluate LMO2 RNA expression by chromogenic in situ hybridization (CISH) in normal tissue and in a series of 82 aLBCL. Methods: LMO2 CISH was performed in formalin-fixed paraffin-embedded tissues, scored by three different methods, and correlated with a transcriptome panel. Results: We obtained statistically significant results correlating the methods of evaluation with LMO2 protein expression and gene expression results. Normal tonsil tissue showed high levels of LMO2, particularly within the light zone of the germinal center. Conversely, in aLBCL, a notable reduction in LMO2 expression was noted, remarkably in cases carrying MYC rearrangements. Furthermore, significant results were obtained through overall survival and Cox regression survival analysis, incorporating International Prognostic Index data alongside LMO2 expression levels. Conclusions: We show a reliable method to identify LMO2 mRNA expression by CISH, effectively capturing many of the reported biologic features of LMO2.

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Low LIM-domain only 2 (LMO2) expression in aggressive B cell lymphoma correlates with MYC and MYC/BCL2 rearrangements, especially in germinal center cell-type tumors

Cited by 3 publications

References 14 publications

Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 3: Mature Leukemias/Lymphomas

Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 3: Mature Leukemias/Lymphomas

Round-robin testing for LMO2 and MYC as immunohistochemical markers to screen MYC rearrangements in aggressive large B-cell lymphoma

Chromogenic LMO2 mRNA ISH Expression Correlates with LMO2 Protein and Gene Expression and Captures Their Survival Impact in Diffuse Large B-Cell Lymphoma, NOS

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