A novel c-kit positive biphenotypic acute leukemia cell line, TMBL-1, carrying a p53 point mutation.
We established and characterized a c-kit positive cell line from the bone marrow of a patient with biphenotypic acute leukemia (BAL). The cell line, designated TMBL-1, carried a His-175 mutant p53. The immunophenotype of the primary leukemia cells at diagnosis was cytoplasmic CD3+, CD7+, CD13+, CD33-, interleukin-7 (IL-7) receptor+ and c-kit -. However, leukemia cells in relapse and TMBL-1 cells were CD33+ and c-kit +. Immunophenotypically, TMBL-1 is a BAL cell line that coexpresses T-lymphoid and myeloid markers which fulfill the criteria of the European Group for the Immunological Characterization of Leukemia. Stem cell factor (SCF), a key regulator of hematopoiesis signaling through c-kit, enhanced the proliferation of TMBL-1 cells. Direct sequencing revealed the conversion at codon 175 of the p53 gene in the TMBL-1 cells. Primary leukemia cells in relapse also carried the same point mutation but not at diagnosis. Moreover, TMBL-1 cells are sensitive to paclitaxel, which could induce p53-independent apoptosis. The biphenotypic features and p53 mutation may be associated with progression to a more malignant type. This cell line may provide new information on the role of SCF in the overlapping area between early T-lymphoid/myeloid cells, and help in the design of new therapies targeted towards p53 mutations.
Suzuki
Shinsuke
S
Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, National Hospital, Kyushu Cardiovascular Center, Kagoshima, Japan. suzuki2@med2.kufm.kagoshima-u.ac.jp
Uozumi
Kimiharu
K
Hanada
Shuichi
S
Lin
Xiao-Yan
XY
Ohno
Nobuhito
N
Takatsuka
Yoshifusa
Y
Takeuchi
Syogo
S
Owatari
Satsuki
S
Takeshita
Taketsugu
T
Arima
Terukatsu
T
D000328:Adult; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000473:pathology*; D008297:Male; D022423:Myeloid Cells / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D019089:Stem Cell Factor; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit; D017239:Paclitaxel