Myeloproliferative Disorders Flashcards
MPN stands for?
Myeloproliferative neoplasms
What kind of cells are affected in MPN?
Erythroid, granulocyte, monocyte, or megakaryocyte precursors
True or false, you can only have one MPN.
False, there is a chance of to have more than one MPN. They can transform into each other.
For MPN, they can transform into what?
AML (most likely) or ALL (rare)
MPN can present as stable chronic disorders which can have _____ phases
acute phases
MPNs can have problems with _____ or ______
thrombosis or hemorrhage
MPNs are origins are ….
from a single pluripotential hematopoietic stem cells
PV is an overproduction of
Red blood cells. It’s described as unregulated proliferation of bone marrow erythroid, granulocytic, and megakaryocytic elements with increasing RBC #’s in peripheral blood
CML is an overproduction of
granulocytes
ET is an overproduction of
Platelets
PMF is an overproduction of
Bone marrow fibroblasts
In PV, RBC morphology is
Normo-, normo- until iron is used up
What diseases are associated with JAK2 mutations?
ET, CIMF, and PV (seen in over 90% of patients)
What does JAK2 role in the body?
A non-receptor tyrosine kinase. It plays an important role for EPO and TPO receptors up to their place on RBC’s surfface.
Stem cells with JAK2 mutations are ______ to erythropoietin apoptosis
Resistant
A diagnosis of PV requires what to be found in the patient?
2 Major criterias
Hgb level of
-above 18.5 g/dL in men
- above 16.5 g/dL in women
Identification of JAK2 mutation
One of the three minor criterias.
- Panmyelosis in bone marrow
- Low serum EPO level
-Autonomous, erythroid colony formation
in what conditions does ruddy face occur?
In PV, it is because of severely increased RBCs show up as pink color under the skin
In what conditions does hypertension appear in?
In PV, because of severely increased RBCs caused by “sludgy” blood
Feeling of fullness can appear in what conditions?
PV and CML due to increased size of spleen putting pressure on stomach. Increased size from increased cell turnover (high uric acid too!)
In CML, there is increased liver size too but not in PV! In CML its called hepatosplenomegaly.
What are the treatment options for PV?
-Therapeutic phlebotomy
-Myelosuppressive drugs (e.g.hydroxyurea) can decrease blood volume and increase iron stores
Note: Drug therapy can transform PV into AML (15% of patients progress into AML). Too much hydroxyurea can cause patient to develop iron deficiency.
Hydroxyurea treatment can put patients at risk for?
Drug is a myelosupressive drug that decrease blood volume and increase iron stores. It can put patients at risk of transforming their disease into AML
Symptoms of PV are?
Ruddy face
Itchy skin
Hypertension
Vertigo
Feeling of fullness
Blurred vision
Headaches
Increase concentration of uric acid
Spleenomegaly
Increased LAP
Serum B12 increased
Iron storage decreased or absent
Normal oxygen saturation
CML is seen mostly in what patient population?
Adults but can CML can happen to any age.
CML symptoms are?
Anemia, fever, excessive bleeding or bruising, malaise, and hepatosplenomegaly.
Describe the Philadelphia chromosome, what kind of mutation is it?
Reciprocal translocation of chromosome 9 and 22. It puts C-ABL oncogene next to BCR increasing the chance of large deletions to happen on either side of the BCR gene.
A patient is diagnosed with CML and 9q34 deletion is found. What is the prognosis for the patient?
The prognosis is bad. The deletion is in the argininosuccinate synthetase gene.
An adult patient’s CBC W/Diff has found
-RBC range: 4.0 x 10^6/μL
-Platelet range: 500 x 10^3/μL
-WBC 350 x 10^3/μL
-3% blast
-3% pros
-24% myelos
-20% metas
-50% segs
A bone marrow smear found the M;E ratio is 15:1
A PCR found the patient has the Philadelphia chromosome.
What doe these test results suggest the patient has?
CML
What are the phases of CML?
Chronic phase
Accelerated phase
Blastic phase
In CML what phase would make the patient respond poorly to therapies?
The accelerated phase. In this phase patient’s symptoms and lab values would increase.
In CML what phase would have blast count to over 20%?
The blastic phase.
-3/4 of CML patients transform from chronic to acute
-CML patients can turn into AML or rarely ALL
True or false, CML is considered CML if the patient is Ph’ negative.
False, Ph’ negative CML patients is CMML
In general, poorer CML prognosis are associated with…
Increased WBCt (>100k / uL)
Increased basophilia
Increased blasts
Presence of any other abnormal cytogenetics
Platelet count very HIGH or very LOW (over 700k / uL or under 150k / uL)
Gleevec medication is a treatment for what disease/condition?
Gleevec is a treatment for CML. that “cures” over 88% of patients in chronic phase
The advent of monitoring for __A___ has now become an important ___B_____ indicator
A - MRD (minimal residual disease)
B - prognostic indicator
Hyperproliferation of bone marrow fibroblasts (in response to neoplastic mutation) causes…
overproduction of GFs
Progressive bone marrow fibrosis means
increased collagen in patients
PMF, CIMF, and MMM has a chance to convert to…
AML
Symptoms of myelofibrosis are?
-Severe hepatosplenomegaly
-Abdominal pain
-Weight loss
-Anemia = Pallor, malaise, and dyspnea
A blood smear from a patient with myelofibrosis would look like?
- Normo- Normo RBC
-Teardrop shaped RBC due to extramedullary hematopoiesis
-Aniso & Poik
-Left shift and doesn’t decrease with disease progression
-Variable platelet count
Dry tap in bone marrow examination is associated with?
Myelofibrosis, AMegL, and HCL
What are treatments for myelofibrosis?
-Chemo
-Steroids
-Splenectomy
-Bone marrow transplant
What are most common complications for myelofibrosis treatment?
Overwhelming infections and massive hemorrhage
What unique thing can differentiate ET from AML, and AMegL?
Platelets are abnormal unless patient is treated with plateletpheresis. The plateletpheresis decreases platelet count temporarily restoring platelet function. In the other diseases their functions are not restored even if platelet count decreases.
How is ET diagnosed?
Exclude other myeloproliferative disorders and systemic illnesses that produce reactive thrombocytosis first. Book pg. 714
What are ET clinical symptoms?
- Abdominal pain
-Epistaxis
-GI bleeding and bleeding after minor dental surgery
-Thrombotic events
What are some differences in lab findings that separate M7 from ET?
-Positive nRBC (there is less or none in ET)
-Rare left shift
-Positive megakaryocyte fragments
What are some differences in lab findings that separate ET from M7?
-No nRBCs or very rare
-Slight left shift
-No megakaryocyte fragments
What are treatment options for ET?
-Myelosuppressive drugs
-IFN-alpha only if myelosuppressive can’t be given
-Plateletpheresis to restore platelet function temp
WHO modifications to MPN categorizes myeloproliferative disorders further into
Ph’ chromosome subtypes
CNL stands for what? What separates it from other subtypes?
Chronic neutrophilic leukemia. It has no metas or myelos
What is the normal range for LAP?
20 - 100
