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Residual juvenile chronic myelogenous leukemia cells detected in peripheral blood during clinical remission
1Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract:
At diagnosis peripheral blood (PB) or bone marrow from patients with juvenile chronic myelogenous leukemia (JCML) have shown two reproducible abnormalities when studied in cell culture: impaired growth of normal hematopoietic progenitors and excessive proliferation of malignant monocyte-macrophage elements. We used these findings to assess quality of treatment response by serially studying PB specimens from four JCML patients (patients 5, 7, 8, and 9) in complete chemotherapy-induced remission. PB readily yielded high numbers of monocyte-macrophage colonies in CFU-C and CFU-GEMM assays when cultured in early remission, and the colonies were cytogenetically proven to have arisen from a malignant clone in patient 9. When studied later in remission, the abnormal cell proliferation persisted in three of the four patients, but in patient 8 PB colony growth resembled controls. Similarly, when PB from patient 8 was studied in liquid culture without using added growth factor, cell proliferation declined identical to controls, whereas PB from the other three patients showed exuberant growth of monocyte-macrophage elements. Patient 8 successfully completed therapy and has been in a long-term, disease-free remission. The other three had recurrent, ultimately fatal disease. The cell cultures have allowed detection of residual abnormal cells that circulate in PB of JCML patients in remission. Although patient numbers were small because of the rarity of JCML, the data suggested that persistence of leukemia cells in these patients had a bearing on clinical outcome.
Insights
Cell cultures of peripheral blood from juvenile chronic myelogenous leukemia (JCML) patients detected residual leukemia cells. Persistent abnormal cell growth in remission predicted poor clinical outcomes and disease recurrence.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Juvenile chronic myelogenous leukemia (JCML) presents with distinct peripheral blood (PB) and bone marrow abnormalities.
- These include impaired normal hematopoietic progenitor growth and excessive malignant monocyte-macrophage proliferation.
- These abnormalities offer potential markers for assessing treatment response.
Purpose of the Study:
- To evaluate the utility of cell culture findings in assessing treatment response in JCML patients.
- To serially monitor peripheral blood specimens from JCML patients in complete remission.
- To correlate the presence of residual leukemia cells with clinical outcomes.
Main Methods:
- Serial peripheral blood (PB) specimens from four JCML patients in complete remission were studied.
- Cell culture assays, including CFU-C and CFU-GEMM, were used to assess hematopoietic progenitor growth.
- Liquid cultures without added growth factors were performed to evaluate monocyte-macrophage proliferation.
- Cytogenetic analysis confirmed the origin of colonies from a malignant clone.
Main Results:
- Early remission PB showed high numbers of monocyte-macrophage colonies, with malignant origin confirmed in one patient.
- Persistent abnormal cell proliferation was detected in three of four patients later in remission.
- One patient (patient 8) showed normal PB colony growth and proliferation, correlating with long-term disease-free remission.
- The other three patients with persistent abnormal cells experienced recurrent, fatal disease.
Conclusions:
- Cell cultures of PB can detect residual leukemia cells in JCML patients even in remission.
- Persistence of abnormal cell proliferation in remission is associated with a higher risk of relapse and poorer clinical outcome.
- This method holds potential for monitoring JCML treatment response and predicting prognosis.