T2 - Neoplasia 13 - Myeloproliferative Disorders And Acute Leukemia/myelodysplastic Syndrome

Front 1

what's the fundamental difference between myeloproliferative disorders and other leukemias/lymphomas? what are our diseases of interest?

Back 1

here, you get blood cells being made irregularly, but they DEVELOP TO THE LAST STEP - so you see lots of "grown up" cells floating around, not a lot of baby cells.

diseases of interest, for sure, are POLYCYTHEMIA VERA,
ESSENTIAL THROMBOCYTOSIS
CML
and here's where it's tricky - maybe myeloid metaplasia, maybe primary myelofibrosis, and leukoblastosis.

Front 2

talk about Polycythemia Vera: who gets it, how can it be treated, what causes it...? other diseases it might be mistaken for?

Back 2

NEED TO KNOW: this is a JAK2 Kinase Mutation!!! recall that the EPO receptor communicates via Jak/Stat - if it's always on, get huge proliferation or RBC's.

usually older patients, lots are asymptomatic, some have Erythromyelia (blood in tissues), pain, hepatosplenomegaly, REALLY HIGH CRITS >60,

can be treated with PHLEBOTAMY, hydroxyurea, aspirin.

high altitude, cancer, high EPO, smoking can all increase RBC's, so watch out.

see NO IRON STORAGE due to all of it being used up.

Front 3

essential thrombocytosis - what might it be mistaken for, what is it, how is it treated? What cells are dividing? what mutation causes it?

Back 3

this is a problem of MEGAKARYOCYTES - see lots of them in the bone marrow.

see platelet counts of 600k or up to 1 million.

patients have splenomegaly sometimes, erythromelagia (burning/throbbing).

treated with aspirin, hydroxyurea, platelet plasmaphoresis. ASPIRIN USED ONLY IF PERSON IS HAVING THROMBIC EVENTS - remember, most people with ET bleed way too much, don't need to further kill their platelets.

note that high platelets can be caused by IRON DEFICIENCY, so need to rule it out.

50% have Jak2 mutation, just like in polycythemia vera.

Front 4

CML - what causes it, who normally gets it? phases?

Back 4

Seen later in life usually. 9:22 translocation causes it in 100% of cases. BCR-ABL fusion.

see a "left shift" in this one, counter to the others (slightly less mature cells, but not as far as other blood cancers).

think BASOPHILIA.

there's a chronic phase, an accelerated phase, and a blast phase:

chronic: lots of semi-mature neutrophils floating around.

accelerated: worsening of symptoms, more immature cell leakage

blast crisis: end stage, people here are going to get AML/ALL and die.

Front 5

what's a "spent phase?"

Back 5

later stage of all the myeloproliferative disorders - bone marrow ends up fibrosed and you get FEWER cells made, lots of problems associated with that.

Front 6

What's primary myelofibrosis? Where does it come from, symptoms, smears, etc...

Back 6

think PAN-CYTOPENIA - a bit like "spent phase," not sure where it comes from. Smears show tear drops (dacryocytes) and EXTRAMEDULLARY HEMATOPOESIS.

bone marrow gets fibrotic, so get extra-marrow making of blood cells (spleen swells up).

hard to treat, people can stay stable for years/die of infection

think 30% have a Jak2 mutation.

Front 7

talk about how lymphomas/leukemias are named, and what separates them

Back 7

first, leukemia = blood, lymphoma = discrete masses.

interested if it's ACUTE or CHRONIC. Acute involves lots of baby cells that are failing to develop (some kind of block to differentiation). these are BLASTS!

Chronic involves lots of mature-ish cells, problem with "disordered proliferation"

whether acute or chronic, ask if it's LYMPHOID (B or T cells) or MYELOID (everything else).

if it's acute and myeloid, maybe AML or MDS. Acute and lymphoid = ALL (B or T cells).

if it's CHRONIC and MYELOID, it's one of our myeloproliferative disorders (CML, ET, P. Vera, Myelofibrosis). If it's CHRONIC and LYMPHOID, could be B or T cell - b = CLL/SLL, hairy cell, myeloma. T = ATCL, LGL, MF/SS.

Front 8

with acute leukemias, are we likely to see too many, too few, or normal number of WBC's?

Back 8

the number of WBC's can go either way with all of them. Maybe too many, too few, etc. BUT WILL SEE BLASTS = immature cells. Blasts are normally only 3%.

generally though, a patient with bleeding, pancytopenia, anemia = acute leukemia.

Front 9

AML - who gets it, typical symptoms, what's seen on smear?

Back 9

more likely as you age, most common acute leukemia of young adults.

SUDDEN ONSET - usually fatigued due to severe anemia, fevers/infections. few if any mature granulocytes, so CAN'T FIGHT OFF INFECTIONS.

lots of BLAST cells and AUER RODS!!!! auer rod = AML, always.

also see granular cells, nucleoli.

Front 10

Which of our acute leukemias has special subsets we should know about?

Back 10

AML - divded into fM groups, separated by FAB and WHO naming system.
Need to know M3 - this is Acute Promyelocytic Leukemia.

It has particular acute problems - including DIC. know that it's a 15/17 translocation! also that it can BE TREATED WITH RETINOIC ACID DERIVATIVES. .

M4 (EOSINOPHELIA) and M5 are seen typically after previous cancer, caused by chemo. see TISSUE INFILTRATION (gross picture of kid with gum tumors)

maybe know M7 is associated with Down's syndrome.

m2 is an 8:21 translocation,

Front 11

ALL - who gets it, what kinds are there, and what's seen on smear? symptoms?

Back 11

acute lymphoblastic leukemia is the most common leukemia in children. can get it as adults, but it's much worse (95% of kids survive, adults not so much).

symptoms are like AML, with the addition of possible CNS involvement (ALL can cross into protected tissues like testis/brain), BONE PAIN, maybe mediastinal masses if T cell lineage.

lymphadenopathy/splenomegaly more common in ALL than AML.

circulating cells are BLASTS, but here they ARE NOT GRANULAR, and certainly don't have auer bodies.

Front 12

ALL - how can we tell between B and T cells? mutations involved? outcomes?

Back 12

B is more common. Involves 12:21 TRANSLOCATION (know this).

T cell can involve the 9:22 translocation like in CML, though it's different and IT IS A BAD OUTCOME predictor.

2-10 years old is ideal...before and after, bad news.

Front 13

What's MDS? Who commonly gets it and what are the usual symptoms?

Back 13

Myelodysplastic syndrome - it's the other acute myelo-derived weirdness. Often turns into its neighbor, AML.

This is "sick marrow," patients are usually 60+. used to be called "pre leukemia"

Anemias, bleeding, infections. Maybe higher MCV's (MACROCYTOSIS) are thought to B12/folat deficiency, but don't respond to typical treatment.

Front 14

What mutations are seen in MDS?

Back 14

monosomy 5, monosomy 7, trisomy 8 are all buzzwords we should associate with MDS. sometimes associated with radiation/alkylating agents.

Front 15

let's do a repeat of the genetic mutations seen in myeloproliferative disorders and acute leukemias:

Back 15

Polycythemia Vera = Jak2

Essential Thrombocytosis = Jak2, 50% of the time.

CML = 9:22

Myelofibrosis = 30% Jak2.

AML = (m3 = acute promyelocytic leukemia = T 15:17)
m4/5 = post-chemo
m7 = downs
m2 = 8:21

ALL = (B cell = 12:21)

MDS = monosomy 5/7, trisomy 8


LYMPHOMAS:
small B cell:
Follicular = 14:18, BCL-2
Mantle = 11:14, Cyclin D up
Marginal = 11:18

Large B cell:
Burkitt's: 8:14

Diffuse, Large cell: BCL-6 mut


T cell:
ALCL: 2:5 translocation