Table 1.
Patients’ characteristics (SM patients) and responses of neoplastic cells to CDK4/CDK6 inhibitors.
| Patient No. | Age | m/f | Diagnosis, SM Variant |
KIT D816V |
Serum Tryptase ng/mL | BM MC Infiltration % | Palbociclib IC50 (nM) | Ribociclib IC50 (nM) | Abemaciclib IC50 (nM) |
|---|---|---|---|---|---|---|---|---|---|
| #1 | 61 | f | ISM | + | 25.4 | 10 | 12.8 | n.t. | n.t. |
| #2 | 42 | f | ISM | + | 22.7 | 2 | 201.2 | 148.3 | 109.2 |
| #3.1 | 61 | m | ISM | + | 17.5 | 3 | 7.2 | 16.7 | 4.5 |
| #3.2 | 62 | m | ISM-AML | + | 26.2 | 5 | 40.3 | 200.2 | 55.2 |
| #4.1 | 70 | m | ISM | + | 83.3 | 20 | 5.7 | n.t. | n.t. |
| #4.2 * | 70 | m | ASM | + | 119 | 5 | 94.4 | 362.1 | n.t. |
| #4.3 | 70 | m | MCL | + | 94.2 | 20 | 12.0 | 252.6 | 13.8 |
| #5 * | 78 | m | ASM-MPN-eo | + | 45.9 | 10 | 67.5 | n.t. | n.t. |
| #6 | 78 | m | ASM-MDS/MPN-u | + | 101.0 | 50 | 4.2 | 75.4 | 159.4 |
| #7 | 75 | m | ASM-MDS/MPN-u | + | 377.0 | 30 | 163.4 | n.t. | n.t. |
| #8 * | 63 | m | ASM-AML | + | 16.5 | 10 | 181.8 | n.t. | n.t. |
| #9 | 91 | m | MCL | + | 49.6 | 10 | 10.4 | n.t. | n.t. |
| #10 | 86 | m | MCL-MDS | + | 180.0 | 30 | 16.8 | 193.9 | 23.7 |
| #11 | 80 | f | ISM | + | 82.9 | 30 | 6.5 | 38.0 | 19.9 |
| #12 | 70 | m | ASM | + | 650.0 | 50 | 81.6 | 119.9 | 135.4 |
| #13 | 57 | m | ISM | + | 85.4 | 5 | 37.0 | 261.7 | 16.9 |
| #14.1 | 70 | m | SM-CMML | + | 374.0 | 20 | 2.6 | 65.8 | 11.1 |
| #14.2 | 70 | m | SM-CMML | + | 66.2 | 2 | 0.25 | 408.0 | 60.4 |
| #15 | 59 | m | MCL | + | 250.0 | 60 | 43.9 | 65.5 | 98.4 |
| #16 | 48 | m | SM-CMML | + | 670.0 | 60 | 28.2 | 134.4 | 33.3 |
| #17 * | 77 | m | SM-AML | + | 30.0 | 10 | n.t. | n.t. | n.t. |
Diagnoses were established according to WHO criteria. The percentage of BM MC infiltration was assessed by immunohistochemistry using antibodies against tryptase and KIT. Primary BM mononuclear cells were isolated and incubated with various concentrations of palbociclib, ribociclib, or abemaciclib at 37 °C for 48 h. Then, proliferation was determined by measuring the uptake of 3H-thymidine and IC50 values were calculated. Abbreviations: WHO, World Health Organization; m: male; f: female; BM, bone marrow; nM, nanomolar; n.t., not tested; IC50, half maximal inhibitory concentration; SM, systemic mastocytosis; ISM, indolent SM; ASM, aggressive SM; MCL, mast cell leukemia, AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; CMML, chronic myelomonocytic leukemia; u, unspecified; eo, eosinophils. * Patient samples used for stem cell viability assays.