High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts

Our plain-English summary of High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts, by T. Kanno, H. Endo, K. Takeuchi, et al (Laboratory Investigation; a Journal of Technical Methods and Pathology, 2002).

The study

• Authors: T. Kanno, H. Endo, K. Takeuchi, Y. Morishita, M. Fukayama, S. Mori
• Journal: Laboratory Investigation; a Journal of Technical Methods and Pathology
• Published: 2002;82(7):893-901
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Methionine aminopeptidase type 2 (MetAP2) is a bifunctional protein that plays critical roles in the regulation of protein synthesis and post-translational processing by (a) protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation by eukaryotic initiation factor 2 kinases and (b) removing the amino-terminal methionine residue from nascent protein. MetAP2 is also known as the molecular target of the angiogenesis inhibitor TNP-470. In addition, it has been recently suggested that MetAP2 has an antiapoptotic function in mesothelioma. To know the pattern of expression of MetAP2 in normal and neoplastic tissues, we raised two specific rabbit polyclonal Abs and examined the pattern of MetAP2 expression in various normal and pathologic specimens. Unexpectedly, we found a very high and selective expression of MetAP2 in germinal center B cells. In the germinal center, dark zone B cells tended to express more MetAP2 than light zone B cells. When 200 malignant lymphomas of various subtypes were studied, a high level of MetAP2 expression, equivalent to that observed in germinal center B cells, was noted exclusively on B-cell lymphoma subtypes that are currently regarded as the neoplastic counterparts of germinal center B cells. The expression of MetAP2 in diffuse large B-cell lymphomas correlated well with that of BCL6 (p < 0.05) but not with that of either CD10 or BCL2. These data suggest that MetAP2 has specific function(s) in germinal center B cells and that the function is shared by neoplastic counterparts of germinal center B cells.

In plain English

This laboratory study from the University of Tokyo did not study asbestos or mesothelioma. It mentions mesothelioma only when describing another research group's work. The authors made two antibodies against a protein called methionine aminopeptidase type 2 (MetAP2). They used them to stain normal human tissues, cell lines and 200 lymphoma (cancer of the lymphatic system) samples. In tonsils and lymph nodes, heavy staining was seen in more than 70% of germinal center cells, which were shown to be B cells. Strong staining was found in 26 of 150 B-cell lymphomas and in none of the T-cell lymphomas or Hodgkin's lymphomas. Strong or weak staining was seen in 14 of 16 follicular lymphomas, 71 of 100 diffuse large B-cell lymphomas and 3 of 3 Burkitt's lymphomas. In 50 diffuse large B-cell lymphomas, MetAP2 staining was associated with staining for BCL6 (p value 0.0275), but not with CD10 or BCL2. The authors wrote that their data suggest MetAP2 has specific functions in germinal center B cells that are shared by the lymphomas that correspond to these cells. They noted there was no evidence yet linking MetAP2 to how lymphomas develop.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory study staining human tissue specimens and cell lines for the MetAP2 protein with newly made antibodies
• Who was studied: 200 lymphoma cases (150 B-cell, 40 T-cell, 10 Hodgkin's lymphoma) plus normal portions of surgically removed human tissues and lymphoma cell lines, studied in Tokyo, Japan; no dates given
• Exposure: No asbestos or other exposure was studied; the study measured levels of the MetAP2 protein in tissues
• Main results:
  • In normal tonsils and lymph nodes, heavy MetAP2 staining was seen in more than 70% of germinal center cells
  • Within germinal centers, cells in the dark zone stained more heavily than cells in the light zone
  • Double labeling showed the heavily stained germinal center cells were B cells (CD20), not T cells (CD3)
  • Strong staining, equal to normal germinal center B cells, was found in 26 of 150 B-cell lymphomas and in none of the T-cell lymphomas or Hodgkin's lymphoma
  • Weak staining was found in 67 of 150 B-cell lymphomas, 14 of 40 T-cell lymphomas, and in Reed-Sternberg cells of 10 of 10 Hodgkin's lymphoma cases
  • Strong or weak staining was seen in 14 (88%) of 16 follicular lymphomas, 71 (71%) of 100 diffuse large B-cell lymphomas and 3 of 3 Burkitt's lymphomas
  • In 50 diffuse large B-cell lymphomas, MetAP2 staining was found in 36 cases and BCL6 staining in 45 cases; the two correlated (Fisher's exact test, p value 0.0275)
  • In the same diffuse large B-cell lymphomas, no statistically significant correlation was found between MetAP2 and CD10
  • No clear association was found between MetAP2 and BCL2 in the lymphoma cases
• The authors' conclusion: The authors wrote that the data suggest MetAP2 has specific function(s) in germinal center B cells and that this function is shared by the corresponding lymphomas (the neoplastic counterparts of these cells)
• Limitations the authors state:
  • The authors stated there is no evidence so far that MetAP2 is involved in how lymphomas develop
  • The authors stated that the function of MetAP2 in germinal center B cells is not yet established
  • The authors cautioned that BCL6, the comparison marker, can be low when the gene is disrupted after chromosomal translocation

Topics

Medical terms in this study, explained in our Lexicon: Angiogenesis, Mesothelioma.

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