Abstract
Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4-4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.
| Original language | English |
|---|---|
| Pages (from-to) | 333-339 |
| Number of pages | 7 |
| Journal | British Journal of Haematology |
| Volume | 129 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2005 |
Fingerprint
Keywords
- Childhood acute myeloid leukaemia
- FAB-M5 subtype
- PTPN11
- SHP-2
- Somatic mutation
ASJC Scopus subject areas
- Hematology
Cite this
Somatic PTPN11 mutations in childhood acute myeloid leukaemia. / Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea.
In: British Journal of Haematology, Vol. 129, No. 3, 05.2005, p. 333-339.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Somatic PTPN11 mutations in childhood acute myeloid leukaemia
AU - Tartaglia, Marco
AU - Martinelli, Simone
AU - Iavarone, Ivano
AU - Cazzaniga, Giovanni
AU - Spinelli, Monica
AU - Giarin, Emanuela
AU - Petrangeli, Valentina
AU - Carta, Claudio
AU - Masetti, Riccardo
AU - Aricò, Maurizio
AU - Locatelli, Franco
AU - Basso, Giuseppe
AU - Sorcini, Mariella
AU - Pession, Andrea
AU - Biondi, Andrea
PY - 2005/5
Y1 - 2005/5
N2 - Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4-4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.
AB - Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4-4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.
KW - Childhood acute myeloid leukaemia
KW - FAB-M5 subtype
KW - PTPN11
KW - SHP-2
KW - Somatic mutation
UR - http://www.scopus.com/inward/record.url?scp=20844439887&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20844439887&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2005.05457.x
DO - 10.1111/j.1365-2141.2005.05457.x
M3 - Article
C2 - 15842656
AN - SCOPUS:20844439887
VL - 129
SP - 333
EP - 339
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 3
ER -