Abstract:
Acute myeloid leukemia (AML) is a
heterogeneous group of malignancies arising
from myeloid stem cell (1,2). The outcome of
AML is ominous most of the time. The prognosis
and treatment of AML (and other leukemias as
well) is dependent on many genetic mutations
and chromosomal aberrations present with the
disease. The classification of AML is also based
on morphology, cytochemistry and genetic
markers. Except for the recurrently defined
chromosomal aberrations such as t(9;21),
t(15;17), inv(l)6, t(9; 11), the majority (more
than 50%) of AML carries normal karyotype
with no underlying recurrent genetic
abnormality (1,2). Two novel mutations
identified in some haematological and non
haematological neoplasia include mutations in
c-KIT gene and NPM 1 gene.
c-KIT is a proto-oncogene which encodes a
transmembrane tyrosine kinase . Ill receptor
(3,4). With its ligand stem cell factor, c-KIT
receptor has been shown to be important for cell
growth, function and survival of cells. It belongs
to the same family of receptors, in Monocyte
Colony Stimulating Factor (M-CSF), PDGF and
FLT 3. It is expressed in many different human
cells including normal haemopoietic precursor
cells, mast cells, germ cells and melanocytes etc.
Its activation leads to a cascade of
phosphorylations in the cytoplasm. It has been
implicated in many none haemopoietic
malignancies including cancers in breast, lung,
ovaries etc (3,4,5,6,). Almost all primary
systemic mastocytosis patients show c-KIT mutations specially one named as c-KIT 816
(D816V). Over-expression of c-KIT receptor in
myeloblasts was observed in 60-80% of AML.
Point mutations of c-KIT gene were exclusively
associated with Core Binding Factor AML
(CBF-AML) which constitutes about 33-45% of
AML and showed higher relapse rate. This could
be related to direct effect of mutated c-KIT gene.
The relapse and worse prognosis in AML sub
types with inv (16) and t (8;21) were associated
with c-KIT mutations even though these
subtypes fall in to good prognosis category
(5-12).
