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Sunday, January 15, 2012

Jumping Genes

Cancer is a disease that has a frightening tinge to it .
It creates apprehension and fear of impending death ,the advances in oncology notwithstanding death does play a big role in Cancer though its shadow is definitely being shortened day by day
We cannot group all Cancer into one it depends on the type ,the site the stage and the other problems associated with the patient ( we call it as comorbidities )
 it also depends on when it was diagnosed , by whom , and what kind of treatment was given and where it was given .
All this goes into what happens to somebody with the big C .

It is preventable to an extent by avoiding obvious risk factors like smoking and use of tobacco  , alcohol use beyond the limits .maintaining a healthy lifestyle with adequate exercise also helps to a great extent .
Preventive and early detection of certain cancers have also brought down the incidence

Finally the myths associated and the fears and barriers of the disease in society  should be broken down

With this morbid introduction let me take you through two discoveries in Cancer research which have made a paradigm shift to its outcomes .

One is in CML or Chronic Myeloid Leukemia and the other is  APML or Acute Promyelocytic Leukemia .
There are great similarities to both these types of Leukemias for once they were thought to be insurmountable mountains as far as treatment was concerned but advances in molecular medicine has made them as pygmy hills to be hopped over today  !

The Time magazine had as its cover when the secrets of  CML was discovered a picture of the capsule used in CML  with the title Cancer Conquered though that proved with time a little overconfident it was not totally wrong


Let us find out what these two epoch making events were

Chronic Myeloid Leukemia is one amongst the four Leukemias ( blood cancer affecting the blood forming cells )
Chronic is the label given for the type of Leukemias with mature cells
 ( fully grown cells ) ( Chronic Myeloid or mature granulated white cells and Chronic Lymhoid Leukemia which had mature lymphoid cells ) and
Acute the type with immature growing cells ( called Blasts )
 ( Acute Lymphoblastic with predominantly lymphoblasts  and Acute Myeloid  Leukemias with myeloblasts or granulated cells )

Amongst the Acute Myeloid Leukemias of which there are several types there was one termed some years back as AML M3 and today called as APML  or Acute Promyelocytic Leukemia ( in short it is the type of Leukemia with predominantly promeylocytes or growing myelocytes )
 The bone marrow is our factory churning out these cells incessantly while millions of cells get killed every other minute ,
all it needs is  a small hitch and then something goes haywire in the assembly line .

Of course each cell has its genes carried in its chromosomes ( it would need a separate blog to explain this so let us leave it at that )
now in the APML affected cell there occurs a quirky switch from normal called Translocation
chromosome 17 in the cell is involved in a reciprocal translocation with the promyelocytic leukemia gene (PML) on chromosome 15, a translocation denoted as t(15;17)(q24;q21).
The fusion of PML and RAR creates a hybrid protein with altered functions.

This protien prevents further growth of promyelocytes into myelocytes and hence promyelocytes are produced in large numbers and are released into the blood stream .

These promyelocytes are abnormal and have toxic granules which burst out into the blood and this causes bleeding and clotting problems ( Diseeminated intravascular coagulation ) this can cause severe problems and can lead to sure death if not treated immediately .
Hence the importance of detecting APML in time which can be done only in centres trained to do so .
The RAR A is Retinoic acid gene ( Vitamin D is Retinoic Acid  ) and when several isomers of Retinoic acid was used in APML it was found that the cis isomer of Retinoic acid called ATRA just reversed the action casued by the fusion of PML RARa  and the promyelocytes started maturing into normal myelocytes !
Ooh la la

Suddenly the most fatal disease turned into most favourable one for treatment of course it wasn’t as simple as that as chemotherapy was also added to ATRA and  had to be continued in several forms for at least two years
 but fact is an incurable type of cancer become completely curable like magic .

Initially when ATRA was discovered it was available only in China and during the Tianamen episode in history  the supplies from China stopped
Roche the famous medical company produced its version and created history .

Similarly in CML there is a fusion between BCR and ABL genes forming a hybrid protien called BCR ABL which caused the mature myelocytes to go uncontrolled

Again a  specific medicne coming under the class Tyrosine kinase inhibitors called imatinib mesylate proved to be the magic pill turning the  CML from a dreaded disease into a manageable one .
Over time more versions of Imatinib came into being  like Dasatanib and Nilotinib

These targetted therapies ( they target only the cancer cells ) and monclonal Antibodies form the backbone of cancer research and treatment today leading us to the inevitable  day when Cancer would be even if not conquered become like say Diabetes or Hypertenison is today .

Let us pray for that day


Joseph Kishore said...

Hi Hari

I read through your writing on cancer which is quite informative although certain terminologies used are beyond my understanding.

Thanks any way and we shall pray for that day which you gave wished for.

umeshjairam said...

As said by Joseph Kishore...

Beena Narayanan said...

Nice to read this blog. Very interesting. Recently, I was attending this conference in Amsterdam where two eminent Drs presented their studies on CML . They were talking about a trial that is going on and in 2016, there will be a breakthrough.

Dasatinib, Nilotinib, then there is Ponatinib which is a multi-targeted TKI whose primary target is BCR-ABL.

Thanks for sharing this Hari and that DAY is already here . As patient advocates, we do advocate this to recipients and there are a lot of them who understand and in turn support others.

Maddy said...

agood one..
a friend of mine has just started on an experimental vaccine after a chemo course for leukemia. lets see how that goes..

Swapna Raghu Sanand said...

In an interview given by Actor Mukesh, he spoke at length about the increasing prevalence of cancer in Kerala. His nephew, a scientist in the US, has undertaken several years studying the pattern and increasing growth of cancer in Kerala. Mukesh says it is shocking how ignorant we have been about its spread and we havent bothered to understand why this is happening faster in Kerala as compared to other states. So, he has undertaken several initiatives for cancer awareness in Kerala.

Your post comes at a time when awareness is more critical than panic.

A popular actress called Mamta Mohandas also talked about how cancer can be overcome by being confident and positive rather than by panicking and imagining life has come to an end.

I've also had the opportunity to meet the famous journalist Leela Menon who mentioned that it is her positive energy that enabled her to overcome the pain and suffering associated with cancer.

Thanks for this post.

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