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MYC protein is a hi...
MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 : a Nordic Lymphoma Group study
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- Rodrigues, Joana M. (author)
- Lund Univ, Dept Immunotechnol, Lund, Sweden.
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- Hollander, Peter (author)
- Uppsala universitet,Cancerimmunterapi
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- Schmidt, Lina (author)
- Lund Univ, Dept Immunotechnol, Lund, Sweden.
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- Gkika, Eirinaios (author)
- Lund Univ, Dept Immunotechnol, Lund, Sweden.
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- Razmara, Masoud (author)
- Akadem Univ Hosp, Dept Clin Pathol, Uppsala, Sweden.
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- Kumar, Darshan (author)
- Aifor Technol Plc, Helsinki, Finland.
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- Geisler, Christian (author)
- Rigshospitalet, Dept Hematol, Copenhagen, Denmark.
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- Grønbæk, Kirsten (author)
- Rigshospitalet, Dept Hematol, Copenhagen, Denmark.;Univ Copenhagen, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Dept Clin Med, Copenhagen, Denmark.
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- Eskelund, Christian W. (author)
- Rigshospitalet, Dept Hematol, Copenhagen, Denmark.;Univ Copenhagen, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark.
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- Räty, Riikka (author)
- Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland.
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- Kolstad, Arne (author)
- Innlandet Hosp Trust, Dept Oncol, Div Gjovik Lillehammer, Gjovik, Norway.
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- Sundström, Christer (author)
- Uppsala universitet,Cancerprecisionsmedicin
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- Glimelius, Ingrid, 1975- (author)
- Karolinska Institutet,Uppsala universitet,Cancerprecisionsmedicin
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- Porwit, Anna (author)
- Lund Univ, Dept Clin Sci, Div Oncol, Lund, Sweden.
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- Jerkeman, Mats (author)
- Lund Univ, Dept Clin Sci, Div Oncol, Lund, Sweden.
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- Ek, Sara (author)
- Lund Univ, Dept Immunotechnol, Lund, Sweden.
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Gronbaek, K (author)
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Lund Univ, Dept Immunotechnol, Lund, Sweden Cancerimmunterapi (creator_code:org_t)
- Ferrata Storti Foundation, 2024
- 2024
- English.
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In: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 109:4, s. 1171-1183
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Abstract
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- The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Rodrigues, Joana ...
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Hollander, Peter
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Schmidt, Lina
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Gkika, Eirinaios
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Razmara, Masoud
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Kumar, Darshan
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Geisler, Christi ...
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Grønbæk, Kirsten
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Eskelund, Christ ...
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Räty, Riikka
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Kolstad, Arne
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Sundström, Chris ...
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Glimelius, Ingri ...
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Porwit, Anna
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Jerkeman, Mats
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Ek, Sara
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Gronbaek, K
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Haematologica
- By the university
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Uppsala University
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Karolinska Institutet