PMC8077377_01
Changes in the treatment of CML and biomarkers. a Changes in leukocyte counts. b Changes in biomarkers. Treatment periods and dosages of dasatinib, ponatinib, and pegylated interferon alpha are shown at the top of the figure. The green, black, red, and blue lines indicate the bcr-abl1 international scale (%), leukocyte counts (/muL), hemoglobin level (g/dL), and platelet counts (/muL), respectively. The yellow triangle indicates the time points when the T351I mutation was detected. All data were shown from the third month from start of dasatinib treatment. PEG-IFNalpha, pegylated interferon alpha; WBC, white blood cell; Hb, hemoglobin; PLT, platelet; IS, bcr-abl1 international scale.
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F1
The hemoglobin and platelet levels dropped below their normal limits (Fig. 1a, b). After administering 14 doses of PEG-IFNalpha, we withdrew the drug because the hemoglobin level reached 3.1 g/dL (Fig. 1b). A few bone marrow aspiration analyses were conducted during the course of treatment, observing a T315I mutation at 9, 25, and 63 months after the start of treatment with dasatinib (Fig. 1b).
T-cell receptor V beta gene repertoire analysis. Naive, effector, and memory CTLs are shown in the upper, middle, and lower panels, respectively. Peripheral blood mononuclear cells were analyzed by flow cytometry using the Beta Mark TCR Vbeta repertoire kit (Beckman Coulter, Tokyo, Japan) according to the manufacturer's instructions. Naive CTLs were defined as the CD8+CD27+CD45RA+ population, effector CTLs were defined as the CD8+CD27-CD45RA+ population, and memory CTLs were defined as the CD8+CD45RA- population. Vb, V beta; Mo, months after starting dasatinib.
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F2
To investigate the cellular immunity, T-cell receptor (TCR) V beta gene repertoire analyses were performed using flow cytometry targeting CD8-positive T cells at several time points (Fig. 2). Although we observed remarkable clonality of the naive and effector CTLs, there has been no obvious clonal expansion of memory CTLs until the present (Fig. 2).