MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2

Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3516-20. doi: 10.1073/pnas.90.8.3516.


During their lifespan, immature cells normally pass through sequential transitions to a differentiated state and eventually undergo cell death. This progression is aberrant in cancer, although the transition to differentiation can be reestablished in inducible leukemia cell lines. This report describes a gene, MCL1, that we isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway. Our results demonstrate that expression of MCL1 increases early in the induction, or "programming," of differentiation in ML-1 (at 1-3 hr), before the appearance of differentiation markers and mature morphology (at 1-3 days). They further show that MCL1 has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation. MCL1 and BCL2 do not fall into previously known gene families. BCL2 differs from many oncogenes in that it inhibits programmed cell death, promoting viability rather than proliferation; this parallels the association of MCL1 with the programming of differentiation and concomitant maintenance of viability but not proliferation. Thus, in contrast to proliferation-associated genes, expression of MCL1 and BCL2 relates to the programming of differentiation and cell viability/death. The discovery of MCL1 broadens our perspective on an emerging MCL1/BCL2 gene family and will allow further comparison with oncogene families.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cloning, Molecular
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Gene Expression / drug effects
  • Humans
  • Kinetics
  • Leukemia, Myeloid
  • Molecular Sequence Data
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / genetics*
  • Poly A / genetics
  • Poly A / isolation & purification
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Poly A
  • RNA
  • Protein-Tyrosine Kinases
  • Tetradecanoylphorbol Acetate

Associated data

  • GENBANK/L08246