PMID- 11133737
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 1
DP  - 2001 Jan 1
TI  - The src homology 2 domain of Bcr/Abl is required for efficient induction of 
      chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis 
      or activation of phosphatidylinositol 3-kinase.
PG  - 4-13
AB  - The effect of mutations in the Src homology 2 (SH2) domain of the BCR/ABL 
      oncogene on leukemogenesis was tested in a quantitative murine bone marrow 
      transduction/transplantation assay that accurately models human 
      Philadelphia-positive B-lymphoid leukemia and chronic myeloid leukemia (CML). The 
      SH2 domain was not required for induction of B-lymphoid leukemia in mice by 
      BCR/ABL. Under conditions where the p190 and p210 forms of BCR/ABL induce fatal 
      CML-like myeloproliferative disease within 4 weeks, p210 SH2 mutants induced 
      CML-like disease in some mice only after a significant delay, with other 
      recipients succumbing to B-lymphoid leukemia instead. In contrast, p190 BCR/ABL 
      SH2 point and deletion mutants rapidly induced CML-like disease. These results 
      provide the first direct evidence of significant differences in cell signaling by 
      the Bcr/Abl tyrosine kinase between these distinct leukemias. Contrary to 
      previous observations, high levels of phosphatidylinositol 3-kinase (PI 3-kinase) 
      activity in primary malignant lymphoblasts and myeloid cells from recipients of 
      marrow transduced with the BCR/ABL SH2 mutants were found. Hence, the decreased 
      induction of CML-like disease by the p210 BCR/ABL SH2 mutants is not due to 
      impaired activation of PI 3-kinase.
FAU - Roumiantsev, S
AU  - Roumiantsev S
AD  - Center for Blood Research, Department of Genetics, Harvard Medical School, 
      Boston, MA 02115, USA.
FAU - de Aos, I E
AU  - de Aos IE
FAU - Varticovski, L
AU  - Varticovski L
FAU - Ilaria, R L
AU  - Ilaria RL
FAU - Van Etten, R A
AU  - Van Etten RA
LA  - eng
GR  - CA57593/CA/NCI NIH HHS/United States
GR  - CA94536/CA/NCI NIH HHS/United States
GR  - HL03310/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Interleukin-3)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/drug effects/enzymology
MH  - Cell Line/drug effects
MH  - Cell Transformation, Neoplastic/drug effects
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Fusion Proteins, bcr-abl/genetics/metabolism/*pharmacology
MH  - Interleukin-3/pharmacology
MH  - Leukemia, B-Cell/etiology
MH  - Leukemia, Experimental/enzymology/etiology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology/*etiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Myeloid Cells/enzymology
MH  - Phosphatidylinositol 3-Kinases/drug effects/metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Point Mutation
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology
MH  - Protein Binding
MH  - Signal Transduction
MH  - Stem Cells/drug effects/enzymology
MH  - src Homology Domains/genetics/*physiology
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - S0006-4971(20)48103-0 [pii]
AID - 10.1182/blood.v97.1.4 [doi]
PST - ppublish
SO  - Blood. 2001 Jan 1;97(1):4-13. doi: 10.1182/blood.v97.1.4.