The gene MIXL1 (Mix1 homeobox-like) encodes a paired class homeobox transcription factor involved in early hematopoietic specification during embryogenesis. Previous studies have shown that MIXL1 gene is expressed in hematopoietic cells during adult life (

Guo et al. Blood 100;1;89–96, 2002
). Furthermore 5′ MIXL1 sequences are a target of retroviral insertion in murine T-cell lymphoma (http:RTCGD.ncifcrf.gov), suggesting a selection advantage for aberrant expression of this gene. However, the status of MIXL1 expression in human lymphomas has not been examined. Using a highly specific antibody, we assessed for MIXL1 protein expression in 14 lymphoma cell lines (9 B-cell and 5 T-cell) by immunobloting. MIXL1 was detected predominantly in nuclear extracts of lysates of all cell lines tested, although at a variable level. We also assessed for MIXL1 protein expression in 126 B-cell and 21 T-cell NHLs of various types, as well as 14 Hodgkin lymphomas using immunohistochemical methods. The results of the immunohistochemical studies are summarized in table 1. Once again, MIXL1 immunoreactivity was primarily nuclear in the tumor cells. Based on distribution data (histogram), a 50% cutoff was selected for high versus low MIXL1 expression. Among B-cell tumors, high expression levels of MIXL1 protein were more frequently detected in high-grade NHL and HL compared with low/intermediate grade NHL (p<0.0001, chi-square test). As a continuous variable, the percentage of MIXL1-positive tumor cells was also significantly higher in high-grade B-cell NHL and HL compared with low/intermediate grade NHL (p<0.0001, Kruskal Wallis test). All Hodgkin lymphomas expressed high levels of MIXL1 with 60% to 100% of neoplastic cells being positive for MIXL1. Most T-cell NHLs also expressed high levels of MIXL1. In contrast, most low/intermediate-grade B-cell NHL and multiple myelomas expressed low levels of MIXL1. Frequent overexpression of MIXL1 gene product in most high-grade B-cell NHLs, HL and T-cell NHLs suggests that aberrant expression of MIXL1 may play a role in proliferation, block of differentiation or both.

Table 1.
HL (n=14)B-NHL (n =126)T-NHL (n =21)
N (%)Low/intermediate gradeN (%)N (%)
Classical HL 12/12(100%) Chronic lymphocytic leukemia /small lymphocytic lymphoma 0/8 (0% T-precursor lymphoblastic leukemia/lymphoma 2/2 (0%) 
Nodular lymphocyte predominance HL 2/2 (100%) MALT-lymphoma 0/8 (0%) Mycosis fungoides/Sezary syndrome 2/2 (0%) 
  Follicular lymphoma 9/24 (38%) Extranodal NK/T-cell lymphoma, nasal type 3/3 (100%) 
  Mantle cell lymphoma 5/34 (15%) Peripheral T-cell lymphoma, unspecified 6/9 (66% 
  High grade  Anaplastic large cell lymphoma 5/5 (100%) 
  B-precursor lymphoblastic leukemia/lymphoma 1/3 (33%)   
  Burkitt lymphoma/leukemia 2/2 (100%)   
  Diffuse large B-cell lymphoma 30/31 (97%)   
  Plasma cell myeloma/plasmacytoma 0/16 (0%)   
HL (n=14)B-NHL (n =126)T-NHL (n =21)
N (%)Low/intermediate gradeN (%)N (%)
Classical HL 12/12(100%) Chronic lymphocytic leukemia /small lymphocytic lymphoma 0/8 (0% T-precursor lymphoblastic leukemia/lymphoma 2/2 (0%) 
Nodular lymphocyte predominance HL 2/2 (100%) MALT-lymphoma 0/8 (0%) Mycosis fungoides/Sezary syndrome 2/2 (0%) 
  Follicular lymphoma 9/24 (38%) Extranodal NK/T-cell lymphoma, nasal type 3/3 (100%) 
  Mantle cell lymphoma 5/34 (15%) Peripheral T-cell lymphoma, unspecified 6/9 (66% 
  High grade  Anaplastic large cell lymphoma 5/5 (100%) 
  B-precursor lymphoblastic leukemia/lymphoma 1/3 (33%)   
  Burkitt lymphoma/leukemia 2/2 (100%)   
  Diffuse large B-cell lymphoma 30/31 (97%)   
  Plasma cell myeloma/plasmacytoma 0/16 (0%)   
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Topics:
burkitt's lymphoma, hodgkin's disease, genes, homeobox, lymphoma, tumor cells, chronic b-cell leukemias, lymphoblastic leukemia, multiple myeloma, antibodies, diffuse large b-cell lymphoma

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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