KIT activating mutations: Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication

Alessandro Beghini, Carla B. Ripamonti, Roberto Cairoli, Giovanni Cazzaniga, Patrizia Colapietro, Francesca Elice, Gianpaolo Nadali, Giovanni Grillo, Oskar A. Haas, Andrea Biondi, Enrica Morra, Lidia Larizza

Research output: Contribution to journalArticle

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Abstract

Background and Objectives. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia. Design and Methods. In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations. Results. Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele. Interpretation and Conclusions. These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.

Original languageEnglish
Pages (from-to)920-925
Number of pages6
JournalHaematologica
Volume89
Issue number8
Publication statusPublished - Aug 2004

Fingerprint

Acute Myeloid Leukemia
Core Binding Factors
Pediatrics
Mutation
Incidence
Trisomy
Chromosomes, Human, Pair 4
Acute Promyelocytic Leukemia
Leukocytosis
Receptor Protein-Tyrosine Kinases
Human Development
Hematologic Neoplasms
Cytogenetics
Chromosome Aberrations
Molecular Biology
Phosphotransferases
Alleles

Keywords

  • Childhood AML
  • Core binding factor leukemia
  • Inv(16)
  • KIT mutations
  • T(8;21)
  • Trisomy 4

ASJC Scopus subject areas

  • Hematology

Cite this

KIT activating mutations : Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. / Beghini, Alessandro; Ripamonti, Carla B.; Cairoli, Roberto; Cazzaniga, Giovanni; Colapietro, Patrizia; Elice, Francesca; Nadali, Gianpaolo; Grillo, Giovanni; Haas, Oskar A.; Biondi, Andrea; Morra, Enrica; Larizza, Lidia.

In: Haematologica, Vol. 89, No. 8, 08.2004, p. 920-925.

Research output: Contribution to journalArticle

Beghini, A, Ripamonti, CB, Cairoli, R, Cazzaniga, G, Colapietro, P, Elice, F, Nadali, G, Grillo, G, Haas, OA, Biondi, A, Morra, E & Larizza, L 2004, 'KIT activating mutations: Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication', Haematologica, vol. 89, no. 8, pp. 920-925.
Beghini, Alessandro ; Ripamonti, Carla B. ; Cairoli, Roberto ; Cazzaniga, Giovanni ; Colapietro, Patrizia ; Elice, Francesca ; Nadali, Gianpaolo ; Grillo, Giovanni ; Haas, Oskar A. ; Biondi, Andrea ; Morra, Enrica ; Larizza, Lidia. / KIT activating mutations : Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. In: Haematologica. 2004 ; Vol. 89, No. 8. pp. 920-925.
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abstract = "Background and Objectives. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia. Design and Methods. In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations. Results. Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1{\%}) adult CBFL cases and 6 of the 49 (12.2{\%}) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele. Interpretation and Conclusions. These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.",
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T1 - KIT activating mutations

T2 - Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication

AU - Beghini, Alessandro

AU - Ripamonti, Carla B.

AU - Cairoli, Roberto

AU - Cazzaniga, Giovanni

AU - Colapietro, Patrizia

AU - Elice, Francesca

AU - Nadali, Gianpaolo

AU - Grillo, Giovanni

AU - Haas, Oskar A.

AU - Biondi, Andrea

AU - Morra, Enrica

AU - Larizza, Lidia

PY - 2004/8

Y1 - 2004/8

N2 - Background and Objectives. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia. Design and Methods. In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations. Results. Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele. Interpretation and Conclusions. These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.

AB - Background and Objectives. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia. Design and Methods. In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations. Results. Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele. Interpretation and Conclusions. These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.

KW - Childhood AML

KW - Core binding factor leukemia

KW - Inv(16)

KW - KIT mutations

KW - T(8;21)

KW - Trisomy 4

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