Nadeem Kizilbash, Jamal Alruwaili, Hassan M. Khachfe, Jaweria Ambreen and Shumaila Asif
Chronic Myelogenous Leukemia (CML) affects the hematopoietic stem cells of the bone marrow. It develops as a chromosomal abnormality due to the presence
of the Philadelphia chromosome carrying the BCR-ABL oncogene. This gene expresses two oncoprotein isoforms, b2a2 and b3a2, produced by the head-to-tail
fusion of p160BCR and p145ABL proteins. The two oncoproteins differ in amino sequence by a 25 residue insertion and a Glu903Asp substitution. In silico
modeling, using the PSIPRED server has provided the secondary structural elements of the two oncoprotein isoforms. This program normalizes the amino acid
sequences generated by PSIBLAST and then uses a neural network to produce the secondary structure. Chronic Myelogenous Leukemia (CML) develops when
a single, hematopoietic stem cell acquires a Philadelphia (Ph) chromosome carrying the BCR-ABL fusion oncogene which gives its progeny an advantage for
proliferation over normal RBCs and allows the Ph-positive clone gradually to displace normal RBCs during hematopoiesis. The abnormal Ph chromosome is
produced by the translocation between chromosomes. The major consequences of Philadelphia translocation is the fusion of the ABL gene on chromosome 9 with
the BCR gene on chromosome 22. The BCR-ABL fusion oncogene encodes new fusion proteins of 190, 210 and 230 kDa molecular weight. The p210BCR-ABL
isoforms have an increased level of tyrosine kinase activity, which is important for the development of the disease. The production of fusion proteins increases
the diversity of proteinprotein binding domains associated with tyrosine kinase activity.
Share this article
Journal of Oncology Translational Research received 93 citations as per Google Scholar report
