Unraveling the Molecular Pathogenesis of Chronic Lymphocytic Leukemia

Allendorf, Daniel J.

doi:10.1001/jama.2010.1940

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Interestingly, CLL/SLL has also been linked to genetic defects on chromosomes 12 and 17, although in different regions than in myxoma, among others [17, 18]. Changes in specific microRNAs, important for posttranslational regulation, have been identified in CLL [19], but no similar work has been done in myxomas. The protein kinase-A (PKA) pathway has been implicated in both diseases as well, [20, 21] with specific PRKAR1A gene mutations reported in patients with the Carney complex [1].…”

Section: Discussionmentioning

confidence: 99%

A Case of Comorbid Myxoma and Chronic Lymphocytic Leukemia: Not Just a Coincidence?

Laird-Fick

Tiwari

Narayanan

et al. 2014

Case Reports in Oncological Medicine

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Background. It is unclear why cardiac myxomas develop. We describe a case of comorbid myxoma and chronic lymphocytic leukemia (CLL) to offer insights into the tumor's pathophysiology. Case. A 56-year-old female with recurrent venous thromboembolism developed embolic stroke. Transesophageal echocardiogram showed a 1.7 × 1 cm sessile left atrial mass at the interatrial septum. Histopathology revealed myxoma with a B cell lymphocytic infiltrate suggestive of a low grade lymphoproliferative disorder. Bone marrow biopsy and flow cytometry of blood and the cardiac infiltrate supported the diagnosis of atypical CLL. She was followed clinically in the absence of symptoms, organ infiltration, or cytopenia. After eighteen months, she developed cervical and axillary lymphadenopathy. Biopsy confirmed B cell CLL/small lymphocytic lymphoma. She elected to undergo chemotherapy with fludarabine, cyclophosphamide, and rituximab, with clinical remission. Conclusions. The coexistence of two neoplastic processes may be coincidental, but the cumulative likelihood is estimated at 0.002 per billion people per year. A shared pathogenic mechanism is more likely. Possibilities include chronic inflammation, vascular endothelial growth factor A, shared genetic mutations, changes in posttranslational regulation, or alterations in other cellular signaling pathways. Additional studies could expand our current understanding of the molecular biology of both myxomas and CLL.

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Section: Discussionmentioning

confidence: 99%

A Case of Comorbid Myxoma and Chronic Lymphocytic Leukemia: Not Just a Coincidence?

Laird-Fick

Tiwari

Narayanan

et al. 2014

Case Reports in Oncological Medicine

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“…Genetic variants within miRNAs or their target sites are one potential cause of the changes in miRNA function observed in cancers (5–8). For example, many patients with B-cell chronic lymphocytic leukemia have three large deletions that cause the loss of miR-15a and miR-16-1, preventing repression of the oncogene BCL2 , and miR-34b and miR-34c, which are activated by TP53 (9,10). Additionally, rs61764370, a single-nucleotide polymorphism that has been associated with lung, ovarian, oral and breast cancer, disrupts a binding site for let-7 in the 3′-untranslated region (3′-UTR) of KRAS , resulting in increased KRAS expression (11–14).…”

Section: Introductionmentioning

confidence: 99%

SomamiR: a database for somatic mutations impacting microRNA function in cancer

Bhattacharya

Ziebarth

Cui

2012

Nucleic Acids Research

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Whole-genome sequencing of cancers has begun to identify thousands of somatic mutations that distinguish the genomes of normal tissues from cancers. While many germline mutations within microRNAs (miRNAs) and their targets have been shown to alter miRNA function in cancers and have been associated with cancer risk, the impact of somatic mutations on miRNA function has received relatively little attention. Here, we have created the SomamiR database (http://compbio.uthsc.edu/SomamiR/) to provide a comprehensive resource that integrates several types of data for use in investigating the impact of somatic and germline mutations on miRNA function in cancer. The database contains somatic mutations that may create or disrupt miRNA target sites and integrates these somatic mutations with germline mutations within the same target sites, genome-wide and candidate gene association studies of cancer and functional annotations that link genes containing mutations with cancer. Additionally, the database contains a collection of germline and somatic mutations in miRNAs and their targets that have been experimentally shown to impact miRNA function and have been associated with cancer.

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“…70 For example, miR-15a and miR-16-1 deletion mutants were unable to block the expression of the BCL2 oncogene in cases of B-cell chronic lymphocytic leukemia. 71 In addition, the rs2910164 mutation in miR-146a has been associated with a number of cancers through increased binding to BRCA1 and other genes. 72,73 Therefore, given its ability to discriminate between mRNA mutants differing by only a single base, this assay (with the aid of total cellular RNA extraction) could potentially be used as a diagnostic platform to detect target RNA sequences associated with a variety of human diseases.…”

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confidence: 99%