Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis.
Analysis of 56 unclustered IgH-CCND1 translocations in mantle cell lymphoma across the ~ 344-kb bcl-1 breakpoint locus demonstrates that half of the CCND1 breaks are near CpG dinucleotides.
As a consequence, the sole cyclin D1 positivity by immunohistochemistry may not be enough to distinguish pleomorphic/blastoid mantle cell lymphoma from diffuse large B-cell lymphoma.
CCND1(+)/MYC(+) DH lymphomas with involvement of 11q13 may also be relatively frequent, the great majority being classified as aggressive variants of mantle cell lymphoma.
Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma.
Median values of normalized cyclin D1 expression determined by real-time quantitative polymerase chain reaction were 1.32 for mantle cell lymphoma, 0.02 for B-cell chronic lymphocytic leukemia, 0.009 for diffuse large B-cell lymphoma, 0.004 for marginal zone lymphoma, 0.002 for follicular lymphoma compared with 0.0003 for reactive lymphoid tissue, and 0.00004 for sorted B cells of healthy donors.
The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.
Recent studies have shown the nuclear expression of sox11 in mantle cell lymphoma, which raises the question about its possible association with t(11;14)(q13;q32), the genetic hallmark of mantle cell lymphoma leading to the overexpression of cyclin D1.
The IGH/CCND1 fusion gene has been reported in many hematologic tumors such as mantle cell lymphoma, chronic lymphocytic leukemia, prolymphocytic leukemia, multiple myeloma, and plasma cell leukemia.
As mantle cell lymphoma is characterized by cyclin D1 overexpression, we assessed for human homolog of MDM4 (HDM4) expression and its effect on p21 in mantle cell lymphoma.
We surveyed lymphomas to determine the range of expression of the mantle cell lymphoma-associated SOX11 transcription factor and its relation to cyclin D1.
Quantitative monitoring of cyclin D1 expression: a molecular marker for minimal residual disease monitoring and a predictor of the disease outcome in patients with mantle cell lymphoma.
The predominant expression of a cyclin D1 mRNA isoform lacking the 3'-untranslated region (Delta3'UTR) is associated with higher total cyclin D1 mRNA levels, increased proliferation and poor prognosis in mantle cell lymphoma, and can be caused by genetic alterations of the 3'UTR region.
Quantitative monitoring of cyclin D1 expression: a molecular marker for minimal residual disease monitoring and a predictor of the disease outcome in patients with mantle cell lymphoma.