Clinical and genetic characteristics of 4 cases with CBL gene mutations
| . | Case 1 . | Case 2 . | Case 3 . | Case 4 . |
|---|---|---|---|---|
| Diagnostic criteria of JMML2 | Compatible | Compatible | Compatible | Compatible |
| At diagnosis | ||||
| Age | 9 mo | 5 mo | 2 mo | 2 mo |
| Leukocytes, ×109/L | 38.5 | 68.6 | 24.3 | 31.9 |
| Immature myeloid cells, % | 22 | 12 | 6.5 | 1 |
| Monocytes, % | 11 | 13 | 13 | 15 |
| Bone marrow blasts, % | 1.5 | 3 | 1.6 | 1 |
| Hemoglobin, g/L | 126 | 113 | 58 | 108 |
| Platelets, ×109/L | 72 | 151 | 13 | 382 |
| Hemoglobin F, % | 9.4 | 7.8 | 10.7 | 17.2 |
| Liver/spleen, length (cm)* | 3/4.5 | 6/10 | 5/4.5 | 1.5/0 |
| Karyotype | Normal | Normal | Normal | Normal |
| BCR/ABL fusion gene | − | − | − | − |
| GM-CSF hypersensitivity | + | + | + | − |
| Treatment (duration) | 6-MP (28 y) | 6-MP+Ara-C (12 y) | 6-MP, UBMT | None |
| Outcome | Alive | Alive | Died of GVHD | Alive |
| At present | ||||
| Age | 28 y | 15 y | 16 y | |
| Leukocytes, ×109/L | 5.8 | 8.6 | 6.3 | |
| Immature myeloid cells, % | 0 | 1 | 0 | |
| Monocytes, % | 5 | 12 | 6 | |
| Hemoglobin, g/L | 117 | 137 | 133 | |
| Platelets, ×109/L | 170 | 136 | 283 | |
| Liver/spleen, cm | 0/0 | 0/0 | 0/0 | |
| Treatment | 6-MP | None | None | |
| CBL mutation type | 1250C>G | 1111T>C | 1255T>C | 1096-1G>T |
| Nail | Ht | Ht | NA | Wt |
| Colony-constituent cells at onset | ||||
| GM, Ho/Ht/Wt | NA | 15/0/0 | 10/6/0 | NA |
| Erythroid, Ho/Ht/Wt | NA | 11/0/0 | 2/7/0 | NA |
| Colony-constituent cells at present | ||||
| GM, Ho/Ht/Wt | 0/4/0 | 15/0/0 | 0/9/2 | |
| Erythroid, Ho/Ht/Wt | 0/9/0 | 15/0/0 | 0/17/1 | |
| CD3+ cells | Ht | Ht | Ht | Ht |
| CD20+ cells | Ht | Ht | Ht | Ht |
| . | Case 1 . | Case 2 . | Case 3 . | Case 4 . |
|---|---|---|---|---|
| Diagnostic criteria of JMML2 | Compatible | Compatible | Compatible | Compatible |
| At diagnosis | ||||
| Age | 9 mo | 5 mo | 2 mo | 2 mo |
| Leukocytes, ×109/L | 38.5 | 68.6 | 24.3 | 31.9 |
| Immature myeloid cells, % | 22 | 12 | 6.5 | 1 |
| Monocytes, % | 11 | 13 | 13 | 15 |
| Bone marrow blasts, % | 1.5 | 3 | 1.6 | 1 |
| Hemoglobin, g/L | 126 | 113 | 58 | 108 |
| Platelets, ×109/L | 72 | 151 | 13 | 382 |
| Hemoglobin F, % | 9.4 | 7.8 | 10.7 | 17.2 |
| Liver/spleen, length (cm)* | 3/4.5 | 6/10 | 5/4.5 | 1.5/0 |
| Karyotype | Normal | Normal | Normal | Normal |
| BCR/ABL fusion gene | − | − | − | − |
| GM-CSF hypersensitivity | + | + | + | − |
| Treatment (duration) | 6-MP (28 y) | 6-MP+Ara-C (12 y) | 6-MP, UBMT | None |
| Outcome | Alive | Alive | Died of GVHD | Alive |
| At present | ||||
| Age | 28 y | 15 y | 16 y | |
| Leukocytes, ×109/L | 5.8 | 8.6 | 6.3 | |
| Immature myeloid cells, % | 0 | 1 | 0 | |
| Monocytes, % | 5 | 12 | 6 | |
| Hemoglobin, g/L | 117 | 137 | 133 | |
| Platelets, ×109/L | 170 | 136 | 283 | |
| Liver/spleen, cm | 0/0 | 0/0 | 0/0 | |
| Treatment | 6-MP | None | None | |
| CBL mutation type | 1250C>G | 1111T>C | 1255T>C | 1096-1G>T |
| Nail | Ht | Ht | NA | Wt |
| Colony-constituent cells at onset | ||||
| GM, Ho/Ht/Wt | NA | 15/0/0 | 10/6/0 | NA |
| Erythroid, Ho/Ht/Wt | NA | 11/0/0 | 2/7/0 | NA |
| Colony-constituent cells at present | ||||
| GM, Ho/Ht/Wt | 0/4/0 | 15/0/0 | 0/9/2 | |
| Erythroid, Ho/Ht/Wt | 0/9/0 | 15/0/0 | 0/17/1 | |
| CD3+ cells | Ht | Ht | Ht | Ht |
| CD20+ cells | Ht | Ht | Ht | Ht |
Liver and spleen sizes (cm) were given in medioclavicular line below the costal margin. Colonies were obtained from PBMCs under stimulation with saturating doses of granulocyte-macrophage colony-stimulating factor, stem cell factor, interleukin 3, and erythropoietin. DNA of individual colonies was directly subjected to a PCR reaction without whole-genome amplification. CD3+ and CD20+ PB cells were separated immunomagnetically. According to flow cytometric analysis, 99% of the isolated cells were CD3+ or CD20+.
mo indicates months; GM-CSF, granulocyte-macrophage colony-stimulating factor; 6-MP, 6-mercaptopurine; y, years; Ara-C, cytarabine; UBMT, unrelated bone marrow transplantation; GVHD, graft-versus-host disease; Ht, heterozygous mutation; NA, not available; Wt, wild-type; GM, granulocyte-macrophage; and Ho, homozygous mutation.