00:00
Our topic is AML, acute
myelogenous leukemia.
00:03
Our focus here will
be, in fact, M3.
00:06
You must memorize if you
haven't already for M3.
00:10
Translocation 15;17.
00:12
And why that’s important to you is
the fact that you can actually treat
a patient with AML, M3 type
with a drug vitamin actually.
00:21
A vitamin derivative known as
ATRA, all trans retinoic acid.
00:25
How is it possible that you
can specifically treat
M3 with ATRA and really
none of the others?
The translocation 15;17 gives rise to in
M3 a retinoic acid receptor alpha, RARA.
00:38
Excuse me?
RARA.
00:42
Receptor for vitamin A
alpha is what that is.
00:46
Retinoic acid receptor alpha.
00:49
Excuse me,
sometimes you got to laugh,
otherwise it makes it quite difficult.
00:54
8;21 is another one.
00:56
This is M2.
00:57
Please know this as being
myeloblastic if I were you,
myeloblastic.
01:01
Promyelocytic is M3.
01:03
Myeloblastic is M2.
01:05
Translocation number is 8;21.
01:11
Genetic abnormalities with AML lead
to defects in stem cell maturation.
01:16
And by definition,
what kind of blasts are you going to
find or what percentage of blasts
are you going to find in
your bone marrow here?
Greater than 20% blasts by
definition, by definition.
01:30
A quick note about myelodysplastic
syndrome and why is it even here?
Myelodysplastic syndrome,
to make your life easier,
you need to think of
this being preleukemic.
01:42
The method by which your patient most
likely develop myelodysplastic syndrome
was the fact the patient was
actually receiving treatment.
01:50
While receiving treatment, unfortunately,
the patient starts developing
myelodysplastic syndrome.
01:56
We call this preleukemic.
01:57
Preleukemic specifically for AML.
02:01
So that means that this patient is
going to have a blast count above 10,
but less than 20, in the middle.
02:09
Let’s take a look.
02:10
May precede AML,
myelodysplastic syndrome.
02:15
Where are you?
In the bone marrow.
02:16
Myelodysplastic syndrome.
02:19
The diagnosis for myelodysplastic syndrome,
because we as clinicians are getting
better for diagnosing our patient,
we are finding tons of
patients that have MDS
only because we are asking
the proper questions
and we know exactly as to
what we’re looking for.
02:34
It's not that incident is increasing
or is the prevalence and such.
02:40
It’s just the fact that we know how
to identify your MDS and by doing so,
you’re actually perhaps might be
preventing a leukemia from taking on.
02:50
Tends to occur in
older individuals.
02:52
Especially common in those
treated with prior chemotherapy.
02:57
Look for that patient.
02:58
Look for that patient please
with myelodysplastic syndrome.
03:02
Presents with --
Well,
the first thing that you’re
going to find because your
bone marrow has been affected
is your pancytopenias.
03:08
The symptom that the
patient is going to first
exhibit is going to be
fatigue and tiredness.
03:14
You, as a clinician though, are
worried about what in this patient?
Neutropenia, therefore you’re
worried about, once again,
susceptibility to infection.
03:24
And now, you do have
shifting to the granulocyte,
but remember please preleukemic.
03:29
So you’re not going to find a
blast count greater than 20,
less than 20,
but pretty damn close.
03:36
Dysplasia in one or more lineages.
03:39
Myelodysplastic syndrome,
it’s getting ready to go on to
acute myelogenous leukemia.
03:48
Now, characterized by
abnormal myeloid blasts.
03:51
Large nuclei and
prominent nucleoli.
03:53
What does this mean?
Let’s get back to task of hand.
03:56
I took a little bit
of pause there
and inserted myelodysplastic syndrome
because I need you to understand
that myelodysplastic syndrome would be--
For you, consider to be
a preleukemic issue.
04:10
Specifically for AML and look for the
patient elderly and prior chemotherapy,
myelodysplastic.
04:17
Now, the blast cell, what is it?
The blast is a large nuclei
and prominent nucleoli.
04:23
It’s a blast.
04:23
It’s huge.
04:25
And on bone marrow aspirate, you'll find
there to be greater than 20% blast with AML.
04:32
Let’s talk about M3 in great detail.
04:34
M3 is a promyelocytic
type of myeloid cell.
04:38
Acute promyelocytic leukemia.
04:41
Cytoplasmic granules with occasional,
occasional, known as Auer rods.
04:46
Now, what are Auer rods?
Auer rods are going to stain for
and look for this description,
peroxidase, okay?
Myeloperoxidase.
04:56
A couple of times when myeloperoxidase
becomes important for you on your boards.
05:01
Myeloperoxidase enzyme,
responsible for creating
your bleach in neutrophil.
05:07
Remember that, myeloperoxidase.
05:09
You go from hydrogen peroxide into
bleach or hypochlorous acid, number one.
05:14
Number two, Auer rod,
stains from myeloperoxidase.
05:19
And number 3,
if I was to tell that your patient maybe,
well, staining for what’s known as your --
We have c-ANCA and p-ANCA, right?
And with this,
one of those ANCAs will be
myeloperoxidase positive.
05:34
Do you know which one?
Good.
05:38
This, in fact, is going to be your p-ANCA,
which is also called MPO
ANCA or myeloperoxidase.
05:46
On the boards for you,
three different times that are important
for you clinically, myeloperoxidase.
05:50
Auer rod is one of them.
05:52
What is it?
It’s a needle-like structure.
05:54
It’s an azurophilic granule
stain with antibody against,
there you have it,
myeloperoxidase.
05:59
Do not forget that, ever.
06:02
Because the description of that
Auer rod might actually come back
to be positive for
myeloperoxidase.
06:06
And if you aren’t paying attention,
you miss a question unnecessarily.
06:09
Now if you see one, it’s
the most likely M3.
06:13
Now, could it be the other AMLs?
Sure it can.
06:17
Sure it can.
06:18
But if your patient has 15;17 translocation
and you find that the treatment for 15;17
with ATRA, all trans retinoic acid,
tends to be effective, then
you this is an Auer rod.
06:32
If you take a look at
this picture here,
you see the needle-like structure
that the arrow is pointing to.
06:37
The needle-like structure that the arrow is
then pointing to, in fact, is an Auer rod.
06:41
It then is positive for
your myeloperoxidase.
06:45
This will be a picture for your
acute myelogenous leukemia.
06:49
And these are the large
nuclei with nucleoli.
06:51
These then represent the
blast, the blast, the blast.
06:55
But this however is actually being
identified in your peripheral blood smear.
07:00
The blast could be located
in your bone marrow.
07:02
They are in fact greater than 20%.
07:07
Here’s my FAB classification.
07:08
I want you to get a decent idea
of the different types
of myeloid cells that
you can create from M0
all the way down to M7.
07:18
Before going on though, I want
you to take a look at M3,
acute promyelocytic leukemia.
07:27
Anything before M3, well you could have
AML type 2 and that’s myeloblastic.
07:32
And then, I want you to move on further.
07:34
Here’s M5, monocytic.
07:37
This is the one that I’d like for you
to know as having gingival hyperplasia.
07:42
Gingival hyperplasia with M5.
07:46
And we have M6, you produce more RBCs.
07:48
By the time you come to M7, platelets.
07:50
I don’t care how you do this.
07:51
From M0 to M7, you’re going
to the myeloid lineage.
07:55
Our focus has been, thus
far, specifically on M3,
translocation 15;17, retinoic
acid receptor alpha.
08:03
The fact that you can find Auer rods,
I gave you all that information.
08:07
Apart from that though, I
cannot guarantee,
they’re not going to ask
you about the others.
08:11
So give yourself a nice
little organization.
08:13
Next up, after M3
will be monocytes.
08:18
M5 is gingival hyperplasia.
08:20
After that is M6, the RBC.
08:22
And by the time you come to M7,
megakaryocyte and if I were you,
I’d make sure that I know what a megakaryocyte
looks like in your bone marrow.
08:31
They like the one a lot.
08:32
So please be able to identify
megakaryocyte in a bone marrow for M7.
08:37
This is a FAB classification for
all acute myelogenous leukemia
and your age group here
is between 15 to 60.
08:47
AML, what’s going on?
Anemia, fatigue, tiredness,
susceptibility to infection, leukopenia,
bleeding, thrombocytopenia,
bone marrow infiltration,
bone pain.
08:58
Things we have talked about already
because you’re invading
the bone marrow.
09:02
Excuse me, actually, the cancer is
originating from the bone marrow.
09:06
So the bone marrow
is infiltrated
and then you’re dumping the
cells into your circulation,
welcome to leukemia, right?
And at some point in time,
it could just then enter the lymph
node and present as lymphoma.
09:20
Yes it can.
09:23
M3 can be treated with ATRA which
stands for all trans retinoic acid.
09:28
Why?
Because the translocation 15;17
will give you, the clinician,
the receptor to then treat it properly
which is retinoic acid receptor alpha.
09:41
How many letters in DIC?
One, two, three.
09:44
Correct.
09:45
DIC could also manifest from M3.
09:50
Once again, one last time, do
not forget what M3 stands for.
09:54
Acute promyelocytic leukemia or
promyelocytic leukemia, PML.
10:00
Don’t lose the question because
you weren't thinking or
or you know I mean like don’t look
at things just unidimensional.
10:08
Look at things as from a
three-dimensional point of view.
10:10
What else could they call this?
How else could they call this?
Oh, I know this information.
10:15
It’s stuck in my head.
10:16
I just need to bring it forward.
10:18
I’m here to try to
help you do that.