A 61-year-old man comes to the office due to tingling of his hands and feet. He has a history of diffuse large B cell lymphoma and has received several cycles of systemic chemotherapy with a regimen that includes cyclophosphamide, doxorubicin, and vincristine. Neurologic examination is notable for a symmetric distal neuropathy in a "stocking and glove" distribution. His electrolytes and fasting blood glucose are normal. The drug responsible for this patient's neurologic symptoms causes cell cycle arrest during which of the following stages?

Question

A 61-year-old man comes to the office due to tingling of his hands and feet.  He has a history of diffuse large B cell lymphoma and has received several cycles of systemic chemotherapy with a regimen that includes cyclophosphamide, doxorubicin, and vincristine.  Neurologic examination is notable for a symmetric distal neuropathy in a "stocking and glove" distribution.  His electrolytes and fasting blood glucose are normal.  The drug responsible for this patient's neurologic symptoms causes cell cycle arrest during which of the following stages?

Quizplus · Accepted Answer

11ec160b_3be0_27a9_9249_c3650cdc5bb8_MD0001_00 This patient with diffuse large B cell lymphoma (most common type of non-Hodgkin lymphoma) has peripheral neuropathy likely due to vincristine. The vinca alkaloids (eg, vincristine, vinblastine) function by inhibiting microtubule formation. Specifically, these agents bind to β-tubulin, thereby preventing polymerization of microtubule proteins. This causes cell cycle-specific cytotoxicity during the M phase of the cell cycle as the replicated chromosomes are unable to align and subsequently unable to segregate into the daughter cells. Of the vinca alkaloids, vincristine is most classically associated with neurotoxicity, which is often dose-related and most commonly presents as peripheral neuropathy. Neurotoxicity likely results from disruption of neuronal microtubules, which are responsible for transporting organelles and other cellular products between the neuronal cell body and the axon terminals. (Choices A, C, D, and E) The following is a description of the phases of the cell cycle: Some chemotherapeutic agents are cell-cycle nonspecific; these include cyclophosphamide, an alkylating agent with side effects that include bone marrow suppression, alopecia, and hemorrhagic cystitis. Educational objective: The vinca alkaloids are cell cycle-specific agents that prevent proper separation of chromosomes into daughter cells during the M phase of the cell cycle. The main dose-limiting side effect of vincristine is neurotoxicity, which commonly manifests as peripheral neuropathy.

A 61-Year-Old Man Comes to the Office Due to Tingling