PMID- 7669664
OWN - NLM
STAT- MEDLINE
DCOM- 19951018
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 90
IP  - 4
DP  - 1995 Aug
TI  - BCL-2 expression by leukaemic blasts in a SCID mouse model of biphenotypic 
      leukaemia associated with the t(4;11)(q21;q23) translocation.
PG  - 855-67
AB  - Acute leukaemia of infancy is associated with abnormalities at chromosome band 
      11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia 
      (MLL), has been identified and has the characteristics of a transcription factor. 
      The BCL-2 gene responsible for blocking of programmed cell death is highly 
      expressed in a number of haematological malignancies, both with and without the 
      t(14;18) translocation. Those without the translocation include acute 
      lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic 
      lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in 
      drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 
      expression is also associated with autonomous growth of leukaemic blasts in 
      culture and predicts a poor prognosis. The SEM cell line, established using blood 
      lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses 
      lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a 
      subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of 
      true biphenotypic leukaemia in the SCID mouse has been established using the 
      SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million 
      cells injected intravenously (i.v.) produce complete replacement of the murine 
      bone marrow by day 30, associated with blood lymphoblastosis and infiltration of 
      the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) 
      analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has 
      confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain 
      reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the 
      MLL-1 gene on chromosome 11 (the main breakpoint region). A further 
      translocation, t(7;13), has been identified. Fluorescent antibody cell sorter 
      (FACS) analysis of tumour material recovered from the SCID-hu model confirms 
      expression of CD19 and CD13 identical to that of the cell line. In addition, 
      BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. 
      BCL-2 expression appears to confer a survival advantage to the blast cells in 
      vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 
      expression may play a role in leukaemogenesis. The model is suitable for the 
      investigation of gene-targeted therapy, including antisense oligonucleotides, 
      directed towards the MLL and BCL-2 genes.
FAU - Pocock, C F
AU  - Pocock CF
AD  - ICRF Oncology Group, Institute of Child Health, London.
FAU - Malone, M
AU  - Malone M
FAU - Booth, M
AU  - Booth M
FAU - Evans, M
AU  - Evans M
FAU - Morgan, G
AU  - Morgan G
FAU - Greil, J
AU  - Greil J
FAU - Cotter, F E
AU  - Cotter FE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow/pathology
MH  - *Chromosomes, Human, Pair 11
MH  - *Chromosomes, Human, Pair 4
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Molecular Sequence Data
MH  - Neoplasm Transplantation
MH  - Polymerase Chain Reaction
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Transplantation Chimera
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - 10.1111/j.1365-2141.1995.tb05207.x [doi]
PST - ppublish
SO  - Br J Haematol. 1995 Aug;90(4):855-67. doi: 10.1111/j.1365-2141.1995.tb05207.x.