Bone marrow large B cell lymphoma bearing cyclin D3 expression: clinical, morphologic, immunophenotypic, and genotypic analyses of seven patients

Watanuki, Jyuri; Hatakeyama, Kinta; Sawada, Takashi; Tatetsu, Hiro; Yoshida, Katsuhiko; Fujii, Soichiro; Mizutani, Minoru; Abo, Toru; Kurimoto, Miwa; Matsuoka, Hiroshi; Matsuno, Fumihiko; Nakakuma, Hideki

doi:10.1007/s12185-009-0382-6

Cited by 5 publications

(3 citation statements)

References 30 publications

(41 reference statements)

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“…Interestingly, a CCND3/IGH translocation has been previously reported in 1 MCL, 8 1 low-grade B-cell lymphoma, 3 splenic lymphomas, and 7 aggressive B-cell lymphomas. [27][28][29][30] Notably, in all of these cases, the CCND3 rearrangement was with IGH and detectable by conventional cytogenetics. Intriguingly, some of these cases expressed CD5, and had blastoid morphology and unmutated IGHV with splenic and leukemic involvement.…”

Section: Discussionmentioning

confidence: 80%

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Martín‐Garcia

Navarro

Valdés-Mas

et al. 2019

Blood

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Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation resulting in overexpression of cyclin D1. However, a small subset of cyclin D1− MCL has been recognized, and approximately one-half of them harbor CCND2 translocations while the primary event in cyclin D1−/D2− MCL remains elusive. To identify other potential mechanisms driving MCL pathogenesis, we investigated 56 cyclin D1−/SOX11+ MCL by fluorescence in situ hybridization (FISH), whole-genome/exome sequencing, and gene-expression and copy-number arrays. FISH with break-apart probes identified CCND2 rearrangements in 39 cases (70%) but not CCND3 rearrangements. We analyzed 3 of these negative cases by whole-genome/exome sequencing and identified IGK (n = 2) and IGL (n = 1) enhancer hijackings near CCND3 that were associated with cyclin D3 overexpression. By specific FISH probes, including the IGK enhancer region, we detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases) in MCL that overexpressed, respectively, these cyclins. A minor subset of 4 cyclin D1− MCL cases lacked cyclin D rearrangements and showed upregulation of CCNE1 and CCNE2. These cases had blastoid morphology, high genomic complexity, and CDKN2A and RB1 deletions. Both genomic and gene-expression profiles of cyclin D1− MCL cases were indistinguishable from cyclin D1+ MCL. In conclusion, virtually all cyclin D1− MCLs carry CCND2/CCND3 rearrangements with immunoglobulin genes, including a novel IGK/L enhancer hijacking mechanism. A subset of cyclin D1−/D2−/D3− MCL with aggressive features has cyclin E dysregulation. Specific FISH probes may allow the molecular identification and diagnosis of cyclin D1− MCL.

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Section: Discussionmentioning

confidence: 80%

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Martín‐Garcia

Navarro

Valdés-Mas

et al. 2019

Blood

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“…A Hinc II fragment of 1.0 kb containing the human IGH joining was used as a probe. Hybridization and washing were performed as previously described [14]. …”

Section: Methodsmentioning

confidence: 99%

Acute Leukemia Showing t(8;22)(p11;q11), Myelodysplasia, CD13/CD33/CD19 Expression and Immunoglobulin Heavy Chain Gene Rearrangement

et al. 2013

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t(8;22)(p11;q11) is a rare but recurrent chromosome translocation that has been reported in 11 cases of myeloproliferative neoplasm or B-acute lymphoblastic leukemia. This translocation results in an in-frame fusion of FGFR1 on 8p11 and BCR on 22q11, and causes constitutive activation of the tyrosine kinase of the BCR/FGFR1 chimera protein. Here, we report the twelfth case of hematological tumor bearing t(8;22)(p11;q11). The bone marrow showed hypoplastic and tri-lineage dysplasia with 24.4% abnormal cells. The abnormal cells were not defined as myeloid or lymphoid morphologically, lacking a myeloperoxidase reaction. Flow cytometric analysis of the bone marrow cells revealed that the abnormal cells expressed CD13, CD33, CD34, and CD19, and that a fraction of the abnormal cells was positive for CD10. Southern blot analysis of the bone marrow cells showed rearrangement of the immunoglobulin heavy chain gene, a genetic hallmark of B-cell differentiation. Previously reported cases with t(8;22)(p11;q11) suggested an association between myeloid and B-lymphoid tumors, whereas other chromosome translocations involving FGFR1 on 8p11 showed a link between myeloid and T-lymphoid tumors. Our observation supports that t(8;22)(p11;q11) might define a dual myeloid and B-lymphoid disorder.

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“…11 Therefore, abnormal expression of CCND3 is associated with many diseases. 12,13,14 However, to date, there is no evidence to confirm the abnormality of CCND3 in SLE.…”

Section: Introductionmentioning

confidence: 99%

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

et al. 2015

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperreactivity. The Toll-like receptor 7 (TLR7) signaling pathway is abnormally activated in SLE B cells. CyclinD3 (CCND3) plays an important role in B-cell proliferation, development, and differentiation. Although previous studies focused on the B cell-intrinsic role of TLR7 for the development of spontaneous germinal centers, the influence of TLR7 on CCND3 in SLE B cells is still not clear. Here, we used a B-cell profiling chip and found that CCND3 was related to SLE and significantly elevated in SLE B cells. Moreover, we determined that the expression level of CCND3 was higher, while miR-15b was significantly lower in the B cells from SLE patients and B6.MRL-Faslpr/J lupus mice compared to normal subjects. Furthermore, we demonstrated that the activation of TLR7 dramatically increased CCND3 expression but significantly decreased miR-15b in B cells in vitro and we identified that CCND3 is a direct target of miR-15b. To further confirm our results, we established another lupus model by topically treating C57BL/6 (B6) mice with the TLR-7 agonist imiquimod (IMQ) for 8 weeks according to the previously described protocol. Expectedly, topical treatment with IMQ also significantly increased CCND3 and decreased miR-15b in B cells of B6 mice. Taken together, our results identified that the activation of TLR7 increased CCND3 expression via the downregulation of miR-15b in B cells; thus, these findings suggest that extrinsic factor-induced CCND3 expression may contribute to the abnormality of B cell in SLE. Cellular & Molecular Immunology

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Bone marrow large B cell lymphoma bearing cyclin D3 expression: clinical, morphologic, immunophenotypic, and genotypic analyses of seven patients

Cited by 5 publications

References 30 publications

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Acute Leukemia Showing t(8;22)(p11;q11), Myelodysplasia, CD13/CD33/CD19 Expression and Immunoglobulin Heavy Chain Gene Rearrangement

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

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