Table 1 Patients with CBL mutation

From: In hematopoietic cells with a germline mutation of CBL, loss of heterozygosity is not a signature of juvenile myelo-monocytic leukemia

 

Hematological phenotype

Gender

Age at diagnosis of hematological disorders (years)

Nucleotidic change

Amino-acid change

Hematopoietic CBL status

Germline CBL status

Pattern of inheritance of the CBL mutation

Other RAS -related mutations a

Endogenous growth of myeloid progenitors

Treatment, outcome (follow up in months)

1

JMML

F

1

c.1111 T>C

p.Tyr371His

Homozygous

Heterozygous

De novo

No

Yes

Relapse after HSCT (LOF)

2

JMML

F

1.1

c.1111 T>C

p.Tyr371His

Homozygous

Heterozygous

De novo

No

Yes

HSCT, CR (51 mo)

3

JMML

F

2.2

c.1111 T>C

p.Tyr371His

Homozygous

Heterozygous

Paternally inherited

No

Yes

HSCT, CR (72 mo)

4

JMML

F

1

c.1228-2 A>G

Splice site

Homozygous

Heterozygous

De novo

No

Yes

HSCT, CR (80 mo)

5

JMML

M

0.5

c.1254 C>G

p.Phe418Leu

Homozygous

Heterozygous

Maternally inherited

No

Yes

No treatment, stable disease (72 mo)

6

JMML

F

2.1

c.1096 -1delGGb

Splice site

Heterozygousc

Heterozygous

De novo

No

Yes

Relapse after HSCT, stable disease (26 mo)

7

JMML

F

2.5

c.1111 T>C

p.Tyr371His

Homozygous

Heterozygous

De novo

No

Yes

Relapse after HSCT, 2nd HSCT, CR (11 mo)

8

JMML

M

4.2

c.1096-1G>C

Splice site

Heterozygous

Wild-type

NA

NF1 (LOH)

Yes

JMML progression and second malignancy (rhabdomyosarcoma). Dead

9

JMML

M

3.9

c.1150T>C

p.Cys384Arg

Heterozygous

Wild-type

NA

PTPN11 Ala72Val

Yes

HSCT, CR (21 mo)

10

Splenomegaly

F

1.6

c.1258 C>G

p.Arg420Gly

Homozygous

Heterozygous

De novo

no

ND

No treatment. Splenomegaly (53 mo)

11

Neutrophilic dermatosis

F

5.7

c.1253 T>C

p.Phe418Ser

Homozygous

Heterozygous

Maternally inherited

No

Yes

Mercaptopurine, Splenomegaly (34 mo)

12

Lympho-histiocytic syndrome

M

2.9

c.1141 T>Gb

p.Cys381Gly

Homozygous

Heterozygous

De novo

No

Yes

No treatment. Auto-immune manifestations (44 mo)

  1. Abbreviations: CR, complete remission; F, female; HSCT, allogeneic hematopoietic stem cell transplantation; JMML, juvenile myelo-monocytic leukemia; LOF, lost of follow-up; LOH, loss of heterozygosity; M, male; mo, month; NA, not applicable; ND, not determined.
  2. aThese mutations were absent from fibroblasts and thus considered as somatically aquired.
  3. bNovel mutation (see Figure 1 for details).
  4. cIn this patient, microsatellite analysis on serial samples confirmed the absence of LOH after 4 months of evolution of JMML (see Figure 1c).
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