Extramedullary leukemia behaving as solid cancer: clinical, histologic, and genetic clues to chemoresistance in organ sites
| Autor: | Audrey C. Papp, Yan Guo, Jianqi Yang, Takayuki Shiomi, Isabel Cunningham, Rory A. Fisher, Bandana Chakravarti, Yu Shyr, Diane Hamele-Bena |
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| Rok vydání: | 2019 |
| Předmět: |
Myeloid
medicine.medical_treatment Breast Neoplasms Pilot Projects Triple Negative Breast Neoplasms Hematopoietic stem cell transplantation 03 medical and health sciences 0302 clinical medicine Breast cancer Antineoplastic Combined Chemotherapy Protocols medicine Biomarkers Tumor Neoplasm Humans Gene Regulatory Networks Breast RNA Messenger RNA Neoplasm Sarcoma Myeloid business.industry Gene Expression Profiling Carcinoma Hematopoietic Stem Cell Transplantation Hematology medicine.disease Prognosis Combined Modality Therapy Neoplasm Proteins Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Drug Resistance Neoplasm Organ Specificity 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female Sarcoma business Invasive Lobular Breast Carcinoma 030215 immunology |
| Zdroj: | American journal of hematologyREFERENCES. 94(11) |
| ISSN: | 1096-8652 |
| Popis: | Recent studies of leukemic tumors in individual extramedullary sites showed they adopt the clinical and metastatic behavior of solid cancers originating in those sites. To elucidate features of leukemic tumors that render them resistant to agents effective against marrow leukemia, we analyzed a series of AML breast tumors by histology, immunohistochemistry, and RNA sequencing. Striking histologic similarities to solid cancers were found: a single-filing architectural pattern virtually identical to that of invasive lobular breast carcinoma and dense desmoplastic keloid-like fibrosis similar to colon, gallbladder, and pancreas carcinomas. Sequencing found 2157 genes significantly downregulated in AML breast tumors compared to normal breast. Comparison to triple-negative breast cancer found 859 genes similarly downregulated. At least 30 of these genes have been associated with poor prognosis in breast cancers. Five were reported in AML marrow studies to correlate with poor prognosis. The findings of this pilot study suggest the seed-and-soil interaction recognized in solid cancer growth may help explain how leukemic cells, in some patients, adopt solid tumor behavior in non-marrow sites. Transformed cells that metastasize from tumor to marrow can impart chemoresistance and be an unrecognized cause of treatment failure and death. Further studies comparing leukemic tumor to simultaneous marrow could potentially identify biomarkers that predict extramedullary resistance and lead to new therapeutic targets. Recognizing the potential for leukemia to adopt solid tumor phenotype, and implementation of body scanning and ablative tumor treatment, could decrease the persistently high rates of marrow resistance and treatment failure. |
| Databáze: | OpenAIRE |
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