What is
AML: A devastating form of blood cancer
characterized by an abnormal increase in the ‘myeloid’ line of white blood
cells. The abnormal cells are called ‘blasts’.
What are the Leukemic Stem Cells?
Recent
findings have shown that AML is initiated and maintained by a small subset of
cells called the Leukemic Stem Cells (LSC).
In other words, these are the cells that give
rise to the leukemia. Just as normal
hematopoietic stem cells (HSCs) give rise to the different blood cells,
leukemia stem cells (LSCs) initiate and maintain the leukemic state. Very
importantly, compared to the rapidly dividing blasts, the LSC are relatively quiescent.
What is the current
treatment and prognosis of AML?
Treatment of
AML is chemotherapy, the main aim of treatment being to clear the bone marrow
of all leukemia cells. The two
chemotherapeutic agents used are Cytarabine (AraC) and an anthracycline
(Doxorubicin or Idarubicin). If
successful, it is said that the patient has achieved remission, which means that there is no detectable AML. This does not mean that the patient is
completely cured, what it means that the disease cannot be detected using
currently available diagnostic methods.
The first phase of treatment is called induction, and is followed by the consolidation phase of intermittent treatment/s. The consolidation phase is done to ensure
that the remission is maintained, and undetectable leukemia cells are also
effectively eliminated.
So what is
the problem?
Unfortunately, there is relapse of the leukemia in many patients; this means that the
disease is back, and usually it’s worse than before!
Therefore AML still remains a mostly fatal disease wherein most patients relapse and die despite achieving an initial complete
remission. Relapse is the major therapeutic obstacle in AML and,
unfortunately, standard therapy has remained largely unchanged over the past
three decades. Bone marrow transplant
may be used in case induction therapy fails, or in case of relapse. However, not all patients are good candidates
for a transplant.
What is the
role of the LSC?
Current chemotherapy for AML (and also most cancers)
targets the rapidly dividing cancer cells, but these drugs are unable to
eliminate the quiescent LSC subpopulation. In other words, current therapy is unable to eliminate the LSC or the root-cause of AML. It has been
seen that patients presenting with a higher proportion LSCs demonstrate
significantly poorer relapse-free survival than patients with low proportions
of LSCs; and LSCs may also contribute to multi-drug resistance, further
complicating the treatment.
Given the high morbidity and mortality of AML patients, it is imperative that we identify new therapeutic approaches to treat this lethal disease. It is hoped that targeting the LSC will help in a better cure for AML.
Given the high morbidity and mortality of AML patients, it is imperative that we identify new therapeutic approaches to treat this lethal disease. It is hoped that targeting the LSC will help in a better cure for AML.
