00:01
Let’s take a look at CML.
00:05
Here is the most
important point.
00:07
Philadelphia chromosome
translocation 9;22.
00:10
Genetically or molecularly,
what is going to give rise to?
It encodes for tyrosine kinase.
00:17
And you know that you can treat your
9;22 by giving your patient imatinib.
00:21
This is a fusion gene
between BCR and ABL.
00:24
The ABL gene produces the tyrosine kinase.
00:27
And that’s important,
important, important.
00:29
That is the target of the
drug that you’re going
to give this patient
known as your imatinib.
00:35
The BCR/ABL fusion protein
results in upregulation
and so therefore, there is uncontrolled
growth of this maturing myeloid cell.
00:42
So when you talk about chronic
myelogenous leukemia,
understand that technically this does come
under your myeloproliferative disorders.
00:51
What does myeloproliferative mean?
Your myeloid cells that are
then increasing in number.
00:58
And when we get to that topic of
myeloproliferative disorders
We’ll be referring to what’s
known as your polycythemia vera.
01:07
We’ll take a look at essential
thrombocythemia, myelofibrosis.
01:10
And we’ll take a look at CML.
01:14
What’s going on with CML?
Uh oh, translocation took place.
01:20
Fusion gene of your BCR/ABL.
01:23
What do you produce too much of?
Good, tyrosine kinase.
01:27
What’s the name of that drug?
Imatinib.
01:31
CML morphology.
01:32
What’re you going to find?
On peripheral blood
smear, you can expect to
find increased numbers
of mature myeloid cells.
01:40
However, you will be paying more
attention to your basophilia.
01:45
Now you find immature granulocytes which
you do not find these huge blasts.
01:49
Take a look at the picture here.
01:50
Do you find huge blasts in the picture?
You can find immature
granulocytes, I’ll give you that.
01:56
Such as myelocytes or metamyelocytes
or bands, but you won’t find blasts.
02:01
Your focus should be on
absolute basophilia.
02:04
What does that mean to you?
That means that my WBC
count is elevated
and you find very high
increase in basophils.
02:11
Remember,
where is your basophil
in the hierarchy?
Basement.
02:20
Who is your patient?
Forty-year-old, on average.
02:23
Insidious,
not always true but
in general correct.
02:29
Symptoms come from the anemia,
splenomegaly,
abdominal fullness.
02:34
So what’s this whole thing
about me not being very,
let’s say, confident about
the insidious onset?
It’s because they can have a really,
really fast paced type of development.
02:49
And that is then called
your blast crisis.
02:51
It’s important for us to pay
attention in that in a second.
02:56
Diseases slowly progresses.
02:59
That’s what you are paying attention to.
03:01
An accelerated phase and the blast crisis.
03:06
Okay, now, it’s easy for
me to say identical to AML
but you’re the one
taking the exam
and obviously you’re going to ask me,
"Well, how can I tell the difference?
Well actually, it’s quite easy.
03:17
In AML, you know the
basics, M0 to M7.
03:21
Say with different myeloid,
FAB classification.
03:24
M3 gives you promyelocytic leukemia,
give you translocation 15;17.
03:28
Gives you Auer rods.
03:29
You don't want to see that
here in blast crisis.
03:32
What’s my topic?
CML.
03:34
Speaking of CML, what’s
the translocation here?
Oh yeah, 9 and 22,
tyrosine kinase, BCR/ABL.
03:41
Right?
How old is your patient?
Well, that part won’t help
you too much, be careful.
03:46
And now, what are they
going to go after?
They’re going to make you think
that, well, this student
only knows about buzz words
and I’m going to give my medical student
a 40-year-old patient with leukemia
and here, she is
going to choose CML.
04:05
No, you’re not.
04:07
You’re going to be smart.
04:08
You’re going to rule things out accordingly
and when you come to the answer choices,
you knew to look for
myeloperoxidase.
04:14
You knew to look for your translocation.
04:17
Maybe you find a gingival
hyperplasia with M5
and you will confidently
choose AML.
04:24
Or you went through
this stem of question.
04:26
Patient was receiving
imatinib and 9 and 22.
04:29
Oh, yeah, we have a blast count
greater than 20% in the bone marrow.
04:34
Oh, this must be
blast crisis of CML.
04:37
Right?
Yes, that’s exactly
what you’ll be doing.
04:41
You won’t miss a question
on leukemia anymore.
04:46
CML and my drug is imatinib.
04:49
We talked about tyrosine kinase.
04:51
Yes, to confine resistance
and that’s scary.
04:54
Look, cancer is behaving
like infections.
04:58
You’ve heard of antibiotic resistance?
Some of these cancers are
so ridiculously intelligent
that they actually will develop
chemotherapy resistance.
05:08
At this point in your learning,
you're left with no choice but
bone marrow transplant, okay?