Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor βreceptor (PDGFβR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2)

Theodora S. Ross, Olivier A. Bernard, Roland Berger, D. Gary Gilliland

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

We report the fusion of the Huntingtin interactin protein I (HIP1) gene to the platelet-derived growth factor βreceptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFβR gene probe demonstrated rearrangement of the PDGFβR gene. Anchored polymerase chain reaction using PDGFβR primers identified chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFβR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFβR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFβR. The reciprocal PDGFβR/HIP1 transcript is not expressed. HIP1/PDGFβR is a 180-kD protein when expressed in the murine hematopoietic cell line, Be/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFβR transforms the Be/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFβR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

Original languageEnglish (US)
Pages (from-to)4419-4426
Number of pages8
JournalBlood
Volume91
Issue number12
StatePublished - 1998

Fingerprint

Leukemia, Myelomonocytic, Chronic
Platelet-Derived Growth Factor Receptors
Fusion reactions
Genes
Proteins
Cells
Huntingtin Protein
Interleukin-3
Gene Fusion
Huntington Disease
Hematologic Neoplasms
Southern Blotting
Polymerase chain reaction
Bone Marrow Cells
Tyrosine
Yeast
Protein-Tyrosine Kinases
Yeasts
Screening
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor βreceptor (PDGFβR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2). / Ross, Theodora S.; Bernard, Olivier A.; Berger, Roland; Gilliland, D. Gary.

In: Blood, Vol. 91, No. 12, 1998, p. 4419-4426.

Research output: Contribution to journalArticle

@article{362d5762b25c4fd19caa6d875b70ae35,
title = "Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor βreceptor (PDGFβR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2)",
abstract = "We report the fusion of the Huntingtin interactin protein I (HIP1) gene to the platelet-derived growth factor βreceptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFβR gene probe demonstrated rearrangement of the PDGFβR gene. Anchored polymerase chain reaction using PDGFβR primers identified chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFβR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFβR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFβR. The reciprocal PDGFβR/HIP1 transcript is not expressed. HIP1/PDGFβR is a 180-kD protein when expressed in the murine hematopoietic cell line, Be/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFβR transforms the Be/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFβR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.",
author = "Ross, {Theodora S.} and Bernard, {Olivier A.} and Roland Berger and Gilliland, {D. Gary}",
year = "1998",
language = "English (US)",
volume = "91",
pages = "4419--4426",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor βreceptor (PDGFβR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2)

AU - Ross, Theodora S.

AU - Bernard, Olivier A.

AU - Berger, Roland

AU - Gilliland, D. Gary

PY - 1998

Y1 - 1998

N2 - We report the fusion of the Huntingtin interactin protein I (HIP1) gene to the platelet-derived growth factor βreceptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFβR gene probe demonstrated rearrangement of the PDGFβR gene. Anchored polymerase chain reaction using PDGFβR primers identified chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFβR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFβR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFβR. The reciprocal PDGFβR/HIP1 transcript is not expressed. HIP1/PDGFβR is a 180-kD protein when expressed in the murine hematopoietic cell line, Be/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFβR transforms the Be/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFβR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

AB - We report the fusion of the Huntingtin interactin protein I (HIP1) gene to the platelet-derived growth factor βreceptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFβR gene probe demonstrated rearrangement of the PDGFβR gene. Anchored polymerase chain reaction using PDGFβR primers identified chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFβR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFβR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFβR. The reciprocal PDGFβR/HIP1 transcript is not expressed. HIP1/PDGFβR is a 180-kD protein when expressed in the murine hematopoietic cell line, Be/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFβR transforms the Be/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFβR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

UR - http://www.scopus.com/inward/record.url?scp=0031864246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031864246&partnerID=8YFLogxK

M3 - Article

C2 - 9616134

AN - SCOPUS:0031864246

VL - 91

SP - 4419

EP - 4426

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -