Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia (CML) following a chemotherapy-induced loss of the Ph¹ chromosome

After intensive chemotherapy, marrow cells of some patients with Philadelphia chromosome (Ph¹) positive chronic myelogenous leukemia (CML) become partially or completely Ph₁-negative. Ph¹-negative. without a second marker for the neoplastic clone, it could not be determined if these Ph¹-negative cells arose from normal progenitors or were still members of an abnormal clone. In the present study, a patient with CML, also heterozygous for glucose-6-phosphate dehydrogenase (G6PD), was studied before and after intensive chemotherapy. Prior to treatment only G6PD type B was detected in the patient's red cells, platelets, and granulocytes, and all unstimulated marrow metaphases had Ph¹. After four cycles of chemotherapy, 76% of marrow cells were Ph¹-negative, and approximately 80% of the granulocytes were nonclonal by G6PD analysis. Thus, the frequency of nonclonal cells by G6PD analysis correlated closely with that of the Ph¹-negative cells. The data indicate that intensive chemotherapy can restore nonclonal and presumably non-neoplastic hematopoiesis in CML.