ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy

Chan, John K.; Lamant, Laurence; Algar, Elizabeth; Delsol, Georges; Tsang, William Y.W.; Lee, King Chung; Tiedemann, Karin; Chow, C. W.

doi:10.1182/blood-2008-03-147017

Cited by 114 publications

(102 citation statements)

References 20 publications

(15 reference statements)

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“…Finally, Chan et al (2008) have described three cases of systemic histiocytosis, presenting in early infancy, expressing ALK or the TPM3-ALK chimeras. It is unclear whether these disorders are indeed true malignancies or due to an aberrant hyperproliferation of macrophages and dendritic cells, driven by the ectopic ALK expression.…”

Section: Alk Fusion Proteinsmentioning

confidence: 99%

Anaplastic lymphoma kinase in human cancer

Barreca

Lasorsa

Riera

et al. 2011

Journal of Molecular Endocrinology

120

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The receptor tyrosine kinases (RTKs) play a critical role, controlling cell proliferation, survival, and differentiation of normal cells. Their pivotal function has been firmly established in the pathogenesis of many cancers as well. The anaplastic lymphoma kinase (ALK), a transmembrane RTK, originally identified in the nucleophosmin (NPM)-ALK chimera of anaplastic large cell lymphoma, has emerged as a novel tumorigenic player in several human cancers. In this review, we describe the expression of the ALK-RTK, its related fusion proteins, and their molecular mechanisms of activation. Novel tailored strategies are briefly illustrated for the treatment of ALK-positive neoplasms.

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Section: Alk Fusion Proteinsmentioning

confidence: 99%

Anaplastic lymphoma kinase in human cancer

Barreca

Lasorsa

Riera

et al. 2011

Journal of Molecular Endocrinology

120

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show abstract

“…11 Subsequently, ALK rearrangements were found in several phenotypically different hematologic neoplasms [12][13][14] and in histogenetically unrelated inflammatory myofibroblastic tumor. [15][16][17][18] Recently, ALK rearrangements and EML4-ALK and KIF5B-ALK fusions were discovered in a subset of non-small cell lung carcinomas; 19,20 proteomics reports suggested a possible TPM4-ALK fusion in esophageal carcinoma; 21,22 and an exon array profiling study demonstrated the EML4-ALK fusion in 2.5% of breast and colon cancers.…”

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confidence: 99%

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

et al. 2011

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Renal cell carcinoma represents a model for contemporary classification of solid tumors; however, unusual and unclassifiable cases exist and are not rare in children and young adults. The anaplastic lymphoma kinase (ALK) gene has recently been implicated in subsets of pulmonary, esophageal, breast, and colon cancers. These findings strengthen the importance of molecular classification of carcinomas across different organ sites, especially considering the evolving targeted anticancer therapies with ALK inhibitors. In the current study of six pediatric renal cell carcinomas, two cases exhibited structural karyotypic abnormalities involving the ALK locus on chromosomal band 2p23. Fluorescence in situ hybridization (FISH) studies were positive for an ALK rearrangement in one case, and subsequent 5 0 rapid amplification of cDNA ends analysis of this tumor revealed that the 3 0 portion of the ALK transcript encoding for the kinase domain was fused in frame to the 5 Keywords: ALK; FISH; fusion gene; renal cell carcinoma; translocation; VCL Renal cell carcinoma has an incidence of 209 000 cases per year and is responsible for 102 000 deaths worldwide annually. 1,2 Approximately 80% of all renal carcinoma cases are currently classified as clear cell, papillary, or chromophobe subtypes with discrete molecular abnormalities characteristic for each group. 2-7 Rare subtypes have also been defined by the 2004 World Health Organization classification and include collecting duct, multilocular cystic, mucinous tubular and spindle cell, medullary, and Xp11.2 translocation-and neuroblastoma-associated carcinomas; each of these subtypes constitutes B1% of all primary kidney epithelial tumors and the three latter subtypes are diagnosed predominantly in children. 8,9 Additional

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“…20,21), and ALK-positive histiocytosis (TPM3; ref. 22) Besides, some ALK fusions have been reported without showing histopathologic evidence: TPM4-ALK in esophageal squamous cell carcinoma (23,24), TFG-ALK in lung adenocarcinoma (25), and EML4-ALK in colon and breast carcinomas (26). The wild-type ALK is mainly expressed in the developing nervous system, and is usually not expressed in other normal tissues (27).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Inflammatory Myofibroblastic Tumor Expressing a Novel Fusion, PPFIBP1–ALK: Reappraisal of Anti-ALK Immunohistochemistry as a Tool for Novel ALK Fusion Identification

Takeuchi

Soda

Togashi

et al. 2011

Clinical Cancer Research

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Purpose: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions. However, detection of some ALK fusions is problematic with conventional anti-ALK immunohistochemistry because of their low expression. By using sensitive immunohistochemistry, therefore, we reassessed "ALK-negative" IMT cases defined with conventional immunohistochemistry (approximately 50% of all examined cases).Experimental Design: Two cases of ALK-negative IMT defined with conventional anti-ALK immunohistochemistry were further analyzed with sensitive immunohistochemistry [the intercalated antibodyenhanced polymer (iAEP) method].Results: The two "ALK-negative" IMTs were found positive for anti-ALK immunohistochemistry with the iAEP method. 5 0 -rapid amplification of cDNA ends identified a novel partner of ALK fusion, proteintyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1 (PPFIBP1) in one case. The presence of PPFIBP1-ALK fusion was confirmed with reverse transcriptase PCR, genomic PCR, and FISH. We confirmed the transforming activities of PPFIBP1-ALK with a focus formation assay and an in vivo tumorigenicity assay by using 3T3 fibroblasts infected with a recombinant retrovirus encoding PPFIBP1-ALK. Surprisingly, the fusion was also detected by FISH in the other case. Conclusions: Sensitive immunohistochemical methods such as iAEP will broaden the potential value of immunohistochemistry. The current ALK positivity rate in IMT should be reassessed with a more highly sensitive method such as iAEP to accurately identify those patients who might benefit from ALK-inhibitor therapies. Novel ALK fusions are being identified in various tumors in addition to IMT, and thus a reassessment of other "ALK-negative" cancers may be required in the forthcoming era of ALK-inhibitor therapy.

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ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy

Cited by 114 publications

References 20 publications

Anaplastic lymphoma kinase in human cancer

Anaplastic lymphoma kinase in human cancer

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

Pulmonary Inflammatory Myofibroblastic Tumor Expressing a Novel Fusion, PPFIBP1–ALK: Reappraisal of Anti-ALK Immunohistochemistry as a Tool for Novel ALK Fusion Identification

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