title: [Chronic myeloid leukemia, biological aspects].
abstract: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a stem cell, involving myeloid, erythroid, megacaryocyte, lymphoid B-cells and "natural killer" cells. The hallmark of CML is the Philadelphia (Ph) chromosome which is a shortened chromosome 22 (22q-) resulting from a reciprocal translocation involving chromosome 9 and chromosome 22, designed t (9;22) (q34;q11). This translocation juxtaposes parts of two genes; ABL on chromosome 9 and BCR (breakpoint cluster region) on chromosome 22. Transcription of the BCR/ABL fusion gene results in an hybrid mRNA that is translated into a 210 kDa or 190 kDa protein, depending on the location of the breakpoint in the bcr region. This protein plays a key role in CML: its tyrosine-kinase activity, that differs from the normal ABL product, may be involved in leukemic cell growth. Nonetheless, the loss of the negative cell growth regulation by c-ABL, or BCR/ABL fusion protein interaction with other cellular genes (such as RAS or c-MYC) could also be involved in CML pathophysiology. A better understanding of the molecular mecanisms of CML could lead to specific treatment, such as tyrosine-kinase inhibitors, synthetic oligodeoxynucleotides, or site-specific DNA-binding proteins designed against BCR/ABL oncogenic fusion sequence.
authors: Département d'hématologie générale, institut Paoli-Calmettes, Marseille, France.
authors: R
authors: R
authors: Costello
authors: R
authors: R
authors: Bouabdallah
authors: D
authors: D
authors: Sainty
authors: J A
authors: JA
authors: Gastaut
authors: J
authors: J
authors: Gabert
mesh_terms: D003001:Cloning, Molecular; D016044:Fusion Proteins, bcr-abl / Q000502:physiology; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000503:physiopathology; D010677:Philadelphia Chromosome; D014178:Translocation, Genetic
chemical_list: D016044:Fusion Proteins, bcr-abl
vernacular_title: La leucémie myéloïde chronique, aspects biologiques.