Match each clinical and pathologic description of a hematologic malignancy with its defining molecular or cytogenetic mechanism.
- An adult patient evaluated for abdominal fullness is found to have massive splenomegaly. Peripheral blood evaluation reveals a leukocyte count of 110,000/µL with a complete spectrum of granulocytic differentiation.Constitutive activation of a chimeric non-receptor tyrosine kinase resulting from a balanced reciprocal translocation.
- A pediatric patient develops a rapidly enlarging, destructive tumor of the jaw. Histopathologic examination of the lesion reveals a uniform population of medium-sized lymphocytes with scattered macrophages containing apoptotic debris.Transcriptional dysregulation due to the relocation of a cellular oncogene adjacent to an active immunoglobulin promoter.
- An asymptomatic older adult is noted to have persistent, generalized lymph node enlargement. Excisional biopsy shows an architectural effacement by tightly packed, uniform follicles lacking normal polarization.Evasion of normal programmed cell death through the pathologic overexpression of an anti-apoptotic mitochondrial protein.
- A young adult is admitted to the intensive care unit with acute hemorrhage and laboratory markers indicating consumptive coagulopathy. Bone marrow analysis demonstrates an accumulation of highly granular myeloid precursors.Maturation arrest of hematopoietic cells caused by a fusion gene that represses transcription of differentiation-inducing target genes.
Cevap
Chronic Myeloid Leukemia pairs with chimeric tyrosine kinase activation; Burkitt lymphoma pairs with oncogene relocation near an immunoglobulin promoter; Follicular lymphoma pairs with overexpression of an anti-apoptotic protein; Acute Promyelocytic Leukemia pairs with a fusion gene causing maturation arrest.
Each hematologic malignancy features a distinct driving mutation that explains its pathologic behavior. CML relies on BCR-ABL1 (tyrosine kinase). Burkitt lymphoma relies on c-MYC (transcriptional activator). Follicular lymphoma relies on BCL2 (anti-apoptotic). APL relies on PML-RARA (differentiation arrest).
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Anahtar Kavram
Molecular pathogenesis of hematologic malignancies and their characteristic translocations.