MYD88 and CXCR4 Mutation Profiling in Lymphoplasmacytic Lymphoma/Waldenstrom’s Macroglobulinaemia

Vinarkar, Sushant; Arora, Neeraj; Chowdhury, Sourav Sarma; Saha, Kallol; Pal, Biswajoy; Parihar, Mayur; Radhakrishnan, Vivek; Chakrapani, Anupam; Bhartia, Shilpa; Bhave, Saurabh Jayant; Chandy, Mammen; Nair, Reena; Mishra, Deepak Kumar

doi:10.1007/s12288-018-0978-1

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…Unfortunately, the analysis of the genomic profile of CXCR4 is not routinely performed in clinics for LPL/WM patients. Importantly, the sensitivity of the used sequencing technique (allele-specific polymerase chain, Sanger, or whole-genome sequencing) and the nature of the analyzed sample (CD19-positive selected lymphocytes or whole BM) represent the most important issues in defining the mutational status of CXCR4 [152,171]. Therefore, universal guidelines are required to standardize the analysis and bring CXCR4 genomic profiling into clinics.…”

Section: Discussionmentioning

confidence: 99%

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

et al. 2020

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Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom’s macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy.

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Section: Discussionmentioning

confidence: 99%

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

et al. 2020

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“…The mutant CXCR4 also aids in the adhesion of B-lymphocytes to the bone marrow stroma resulting in the hypercellular, plasmacytic bone marrow of WM. 9 , 11 - 13 …”

Section: Discussionmentioning

confidence: 99%

“…The mutant CXCR4 also aids in the adhesion of B-lymphocytes to the bone marrow stroma resulting in the hypercellular, plasmacytic bone marrow of WM. 9,[11][12][13] WM has an incidence of approximately 3 cases per one million people per year. About 1400 new cases are diagnosed in the United States per year, comprising of 2% of all cases of non-Hodgkin's lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Blurry Vision as a Presentation of Waldenström’s Macroglobulinemia: A Case Report With Review of Current Management

Adams

Jetly-Shridhar

Tran

et al. 2022

Journal of Investigative Medicine High Impact Case Reports

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A patient was diagnosed with Waldenström’s macroglobulinemia (WM) after the initial findings of anemia and ophthalmological findings of retinal hemorrhage. Upon further workup, the patient was found to have an IgM predominant monoclonal gammopathy on serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP). This highlights the need for open communication between different specialties, streamlining rapid and accurate diagnosis. Also highlighted are the unique pathophysiological changes involved in the development of WM. A patient’s primary complaint was blurry vision. After the patient was noted to have a monoclonal gammopathy on SPEP, bone marrow biopsy was performed. The bone marrow biopsy findings were consistent with lymphoplasmacytic lymphoma (LPL). The patient received plasmapheresis and chemotherapy. The disease course is described. The patient saw rapid improvement in all lab abnormalities after the beginning of the appropriate therapy of plasmapheresis and chemotherapy. Remission is common with WM. Regular follow-up with this patient is important.

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“…CD20 demonstrated that the lymphoma comprised approximately 70-80% of the marrow cellularity while CD138 demonstrated a substantial plasma cell compo-approximately 90% of LPL or WM have MYD88 L265P mutations [1]. Mutations in CXCR4, and ARID1A have also been described [6][7][8]. The diagnosis of LPL is mainly based on histopathologic evaluation of involved tissues, immunophenotypic studies and exclusion of other small B cell lymphoid neoplasms with plasmacytic differentiation.…”

Section: Case Reportmentioning

confidence: 99%

Widespread Multi-Organ Involvement by Lymphoplasmacytic B-Cell Lymphoma in a Patient with Multiple Comorbidities: A Case Report

Oluwaseyi¹,

Kaur²,

Nusrat³

et al. 2019

Int J Pathol Clin Res

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Lymphoplasmacytic lymphoma (LPL) is an uncommon B-cell non-Hodgkin lymphoma in which the affected tissue, usually bone marrow, is infiltrated by small lymphocytes, plasmacytoid lymphocytes, and plasma cells. The lymph nodes, spleen and other tissues/organs in the body are less commonly infiltrated by the neoplastic cells. The clinical course of LPL is indolent although some studies report a more aggressive course and adverse outcomes especially in patients with other primary malignancies including skin cancers. We report an unusual finding of widespread multi-organ involvement by LPL in a 69-year-old male with multiple comorbid conditions and malignant melanoma. He initially presented to the hospital three years ago with hepatosplenomegaly and lymphadenopathy. Pathologic work-up including bone marrow evaluation confirmed the diagnosis of LPL. He was also diagnosed with Waldenström macroglobulinemia. Patient received chemotherapy and was well until about eight months ago when he re-presented with abdominal discomfort from a possible spontaneous bacterial peritonitis. However, during his hospital admission, he developed multiple complications including atrial fibrillation with rapid ventricular rate, persistent hypotension and decreased urinary output. He deteriorated despite active management and was transitioned to comfort care. He was later pronounced dead. Autopsy showed involvement of multiple tissues and organs including the peritoneum, parathyroid glands, heart, and brain by the patient's known B-cell lymphoma. There was extensive involvement of the bone marrow, spleen, liver and multiple lymph nodes. Histologic sections taken from the involved tissues and organs revealed infiltration by small B-cells with plasmacytoid lymphocytes and plasma cells. Sections from the scalp lesions showed in-situ and invasive malignant melanoma with involvement of the left lung.

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MYD88 and CXCR4 Mutation Profiling in Lymphoplasmacytic Lymphoma/Waldenstrom’s Macroglobulinaemia

Cited by 6 publications

References 23 publications

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

Blurry Vision as a Presentation of Waldenström’s Macroglobulinemia: A Case Report With Review of Current Management

Widespread Multi-Organ Involvement by Lymphoplasmacytic B-Cell Lymphoma in a Patient with Multiple Comorbidities: A Case Report

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