leukemia

 Chronic Myeloid Leukemia (CML) Pathogenesis, Symptoms and Treatment

Hey everyone and this is one type of chronic myeloid leukemia or CML and this is where we're going to talk about how we can distinguish this type of leukemia from other types of leukemia we're also going to talk about the pathogenesis of ,CML involving the Philadelphia chromosome. and we're also going to talk about the signs and symptoms and treatment of CML so chronic myeloid leukemia is one type of leukemia and its name allows us to distinguish it from other types of leukemia.

it is a Milo proliferative disorder that presents with increased granular acidic cell line proliferation granular acidic cells are neutral folds and that's where the term Milo it actually comes from. And these cells still have the ability to differentiate so they can be differentiated mature neutral films that's where the term chronic comes from.

And if we were to take a look at a peripheral blood film we can see a lot of mature white blood cells a lot of mature neutral films and we can tell that they're mature because. their nucleus is large in proportion to ,their  so that's what chronic myeloid leukemia is high levels of mature neutrals so a quick approach to determining the type of leukemia again if we see increased white blood cells often very high.

And they're mature white blood cells that means it's a chronic leukemia and it's pmns or neutral cells that mean it's Milo so it's CML that is a ,quick ,approach to determining. that leukemia is actually a chronic mile away leukemia. so the epidemiology of CML generally can occur any age but most commonly occurs in middle age to older adults and generally. ages between sixteen sixty five years so the path of physiology of CML has to do with what we call the Philadelphia chromosome.

In the Philadelphia chromosome is the product of chromosome nine and chromosome twenty two translocation so what happens is that. On chromosome nine we have a proto oncogene known as c able or just able and this piece of chromosome nine ,can ,be popped off.

And can be swapped for a piece on chromosome twenty two so a translocation and what can happen is the piece here ,from chromosome nine can be. put onto chromosome with the gene able right next to the gene bcr. so after the chromosome swap pieces with each other can lead to a change chromosome twenty two what we call a Philadelphia chromosome with the genes bcr and able ,next to each other.

and this leads to the formation of a fusion gene known as bcr able which can produce a new protein ,also ,called ,bcr ,able .and. the problem with this protein is that it is an act of tires and kindness there is no regulation on this protein and that's not what we want we want to have proper regulation. and what happens is because this is continuously active this protein can actually activate.

jack staff pathways and ras raf mek erk pathways both of which lead to increase in cell survival and proliferation not what we want. so that's the path of physiology of cml. so CML presents in about three different clinical phases the first one is what we call chronic phase and chronic phase is where majority of individuals are diagnosed and it's ,around ,eighty ,eighty ,five percent.

And this is when they present with less than ten percent of glass cells. they may have slightly increased e. o.c. inoculates and basil fills at this stage but generally ,the ,stage ,is ,often ,asymptomatic. the next phase is accelerated phase and this is one. neutrophil differentiation becomes impaired remember I said that neutrophil still had the ability to differentiate while in this phase that differentiation ,ability ,starts ,to ,become impaired. and this is when we have about ten to nineteen percent of circulating blood cells.

And we also see it increase in basic files at this time. the increase in basic fill count can actually lead to a pure r. ,it is ,so itching. And we also start to see throne beside opinion at this time because some of the cells in bone marrow begin to crowd out other cells and generally we start to see constitutional symptoms in splendor legally in this. phase as well. and the splendor megalith is caused by an increase in extraordinary humidor policies what that means is that.

because the bone marrow starts to become crowded out by white blood cells. other parts of the body have to kind of make up for it in order to keep producing enough red blood cells so the spleen starts to produce red blood cells. um as an extraordinary process. the third phase is what we call a blast crisis. this is when there are greater than twenty percent of blood cells. and blast sells themselves again failed a different sheet. and oftentimes this is when CML can convert to another type of leukemia oftentimes it's acute mileage leukemia so.

um less often a l l. so what are the signs and symptoms of CML again most individuals ,at ,diagnosis ,are ,asymptomatic. phase but when they become symptomatic there are a few main symptoms and signs I want you to remember.

splendor r Maggie is one of the biggest ones and splendor Maggie is the enlargement of spleen this is the most common physical ,finding ,in ,c m l. and it presents with early society so they get full a little quicker than they used to so you can imagine if you're having an increased spleen it starts to push up against your stomach. and you can't eat as much that's why you get early satiety.

and you also can get left upper quadrant pain simply because of the enlarging of the tissue another common finding which is actually several ,symptoms are the constitutional symptoms. and in CML  they're often mild these can include fatigue Malays fever weight loss excessive sweating so they just generally don't feel well.

that ,is ,not right. and another sign that's interesting with CML is tenderness over the lower sternum and this is ,because ,of expanding bone marrow. symptoms that aren't as specific for CML include anemia simply because the bone mirrors being crowded out there can be bleeding due to thermal cylinder there can be pure ,righteous ,due to increased. Uh basal fills. there can be lugo stasis and there can be pre episode in males for investigations and diagnosis of cml.

again we look at a c b c we have high white blood cell count we have high basil cell count and we often can have decrease in red blood cells or ,the ,anemic ,and ,their thermodynamic. on preferable film like that we talked before. the preferable film is used to determine if it's mature or immature white blood cells and in this case its mature white blood cells.

And a bone marrow biopsy is used to determine the percentage of blast cells so we can categorize what phase they're in. and for diagnosis the diagnosis is quite simple for c.m.l. it's .just. having evidence of bcr able fusion product or Philadelphia chromosome they can use mutual fluorescence and ,other ,tests to determine. this if there is a bcr able fusion product treatment. is with a madam ib and the madam ib is targeting that tire zine kindness so it's a tyrosine kinase inhibitor and this is kind of easy for.

remembering because CML is always a magnetic so we always use a magnetic retreat. there are second generation inhibitors of bcr able or second generation tkis or tires inhibitors due to drug resistance to.

these include the satin hib and milo to nib so what happens generally is a patient gets ,treated with a maddening. and what happens is the cancer can mutate. and can actually mutate resistance to imaginative so that bcr able protein can actually mutate to .avoid. uh inhibition by a maddening so this is why we can move on to using some of these other second generation inhibitors. and just to quickly talk about prognosis.

to determine prognosis for patients with CML we can use a couple different scores we can use a so-called prognostic score which looks at spleen size percentage blasts age. platelet count and a kind of a newer score that's been used to determine the efficacy and prognosis with imaginative treatment is the Utah score. a bit simpler because it only looks at a couple of different things again screen size and percentage base of fills ,so ,these both can.

give you prognostic scores there are online calculators for these to help you with a prognosis for patients with cml. Come and learn to read these valuable things often.