We experienced two patients with mixed phenotype acute leukemia with t(9;22)(q34;q11.2); BCR-ABL1 according to the WHO classification 2008. The type of BCR/ABL1 was major in both patients, and the chimeric gene was also detected in neutrophils from peripheral blood by the fluorescence in situ hybridization technique. Patient 1 was a 59-year-old Japanese woman, and patient 2 a 45-year-old Japanese man. They had both developed leukemia suddenly. Their leukemic blasts expressed B cell and myeloid cell antigens, but concomitantly in patient 1 (biphenotypic) and separately in patient 2 (biclonal). Percentages of BCR-ABL1-positive neutrophils were 98% and 89%, respectively. Both patients received an imatinib (600 mg/day)-combined Hyper-CVAD regimen as induction therapy, followed by treatment with dasatinib (140 mg/day). MEC therapy was also applied between these two treatments in patient 2. At present, patient 1 has obtained complete molecular remission quantitatively and qualitatively, and patient 2 only quantitatively. Considering their acute onsets with no prior history of chronic myelocytic leukemia (CML), they were both diagnosed as having acute leukemia with Ph1, but not blastic crisis of CML. In this tyrosine kinase inhibitor era, it has become more difficult to differentiate these two types of Ph1-positive leukemia development.

Herein, we report the case of a 56-year-old man with composite lymphoma (CL) comprised of mantle cell lymphoma (MCL) and follicular lymphoma (FL). Six months after developing a right brachial tumor, he was diagnosed as having grade 3 FL with normal-size mantle zone. Simultaneously, advanced stage MCL with a diffuse growth pattern in a sigmoid colon tumor and abnormal lymphoid cells in bone marrow were observed. Thereafter, the right brachial tumor was re-examined and its mantle zone cells were immunophenotypically positive for cyclin D1 (CCND1) and cytogenetically positive for the IgH-CCND1 fusion gene. Consequently, he was diagnosed with composite lymphoma (CL) comprised of FL and MCL. As MCL and FL may form CL, the possible complication of MCL should be considered and steps taken to detect MCL.

Misrepair of DNA damage induced by ionizing radiation is a potential cause of carcinogenesis following exposure to radiation. Radiation exposure increases the incidence of the same types of mutations that occur spontaneously in a given population. A high incidence of DNA double-strand breaks is characteristic of damage by ionizing radiation compared with those induced by other environmental mutagens. In China, residents living in areas with high level background radiation(6mSv/y) had a significantly higher frequency of dicentric and ring chromosomes compared to that for the residents living in the control areas(2mSv/y). Radiation-associated increases in risk were seen for most sites. Gender-averaged excess absolute risk rates estimated at age 70, after exposure at age 30, differ in the sites, and the risks of gastric cancer, breast cancer, colon cancer, and lung cancer were highly increased, in that order. Latent periods for the development of leukemia and thyroid cancer after radiation exposure at ages younger than 18 were shorter compared to those for other solid cancers.

Epigenetic therapy is highly anticipated as a next player to molecular target drugs. Epigenetic abnormalities are maintained even after a somatic cell division, and can be causally involved in carcinogenesis. Recent cancer genome analysis revealed that a significant fraction of cancers cannot be accounted for only by mutations of known protein-coding genes, and that mutations of epigenetic genes are unexpectedly frequent. DNA demethylating drugs and histone deacetylase inhibitors are already approved, and many next-generation epigenetic drugs are under development. Application of epigenetic therapies to solid tumors is being attempted, and a promising result is available for non-small cell lung cancers. Right patients, right doses, and right combinations are key to further success, and can be done based on recent progresses in mechanistic analyses.

The patient involved in case 1 was an approximately 50-year-old woman with left lung adenocarcinoma (cT4N0M1), pleural dissemination, and carcinomatous pleural effusion. Chemotherapy with cisplatin and S-1 was administered as first-line therapy, and after the second course of chemotherapy, the thoracic drainage tube could be removed. Thereafter, the patient's performance status (PS) improved to 0. However, brain metastasis was detected, with symptoms of dizziness and headache, and activities of daily living (ADL) decreased, resulting in deterioration of the PS to 4. Although epidermal growth factor receptor (EGFR) mutation status was unknown, erlotinib (150 mg/day) was administered, which was evidently effective in reducing brain metastasis and resulted in recovery of the PS to 0. The patient involved in case 2 was an approximately 50- year-old man with a complaint of coughing. Chemotherapy with 4 courses of cisplatin and pemetrexed was administered as first-line therapy, and local radiation therapy (66 Gy) followed by 4 courses of docetaxel was administered as second-line therapy. However, the patient showed progressive disease (PD) and emergence of brain metastasis. Although the patient was negative for EGFR mutation, erlotinib (150 mg/day) was initiated as third-line therapy. Chemotherapy was successful and the local lesions were under control. We performed left pneumonectomy to improve quality of life (QOL), which had decreased because of repeated obstructive pneumonia caused by the tumor. Owing to the surgery, the patient was able to maintain a PS of 0 and a favorable QOL, while the administration of erlotinib was continued. In conclusion, erlotinib functions effectively in 3 ways. First, it can be used for emergency administration in cases of unknown EGFR mutation status. Second, its use facilitates the performance of salvage surgery in patients who are EGFR mutation negative. Finally, erlotinib is expected to be effective in the treatment of brain metastasis.