The most likely diagnosis in this patient is chronic myeloblastic leukemia (CML). Imatinib is a tyrosine kinase inhibitor that specifically targets the bcr-abl fusion protein responsible for CML.
In this elderly patient with systemic symptoms, splenomegaly, and hematologic abnormalities, hematologic malignancies including leukemias and lymphomas should be suspected. These disorders are supported by the abnormal leukocytes seen on the peripheral blood smear. The presence of the 9;22 chromosomal translocation (hinted at in the stem) indicates that this patient has CML. The 9;22 translocation – known as the Philadelphia chromosome – creates a novel fusion tyrosine kinase (bcr-abl). The increased activity of this fusion protein results in high rates of cell division and inhibition of apoptosis. Clinically, CML is often asymptomatic but can present with systemic symptoms (e.g., fatigue, weakness, night sweats, weight loss) and splenomegaly. Imatinib is a targeted therapy that specifically blocks activity of the bcr-abl fusion protein.
Figure A demonstrates characteristic histologic findings in CML. Note the abundant dysplastic leukocytes (predominately of myeloid lineage) with irregular nuclei and a high nucleus-to-cytoplasm (N:C) ratio.
Answer 2: Rituximab is an anti-CD20 monoclonal antibody that is used to treat hematologic malignancies, transplant rejection, and autoimmune disorders.
Answer 3: Trastuzumab is an anti-HER-2 monoclonal antibody used to treat HER-2-positive breast cancer.
Answer 4: Similar to imatinib, erlotinib is a receptor tyrosine kinase inhibitor. It specifically targets the epidermal growth factor receptor (EGFR) and is used to treat multiple neoplasms including non-small cell lung cancer and pancreatic cancer.
Answer 5: Etanercept is a TNF receptor that binds to and sequesters pro-inflammatory TNF. It is used to treat rheumatologic and autoimmune conditions such as rheumatoid arthritis, psoriasis, Crohn disease, and ulcerative colitis.
Chronic myelogenous leukemia is caused by a 9;22 translocation (Philadelphia chromosome) that creates the bcr-abl fusion protein. Imatinib is a targeted therapy that specifically inhibits the bcr-abl tyrosine kinase.