Myeloproliferative Neoplasms (MPNs) Flashcards
Define myeloproliferative neoplasm
Clonal disorder of HSC caused by genetic mutations. This leads to reduced negative feedback, thus malignant overproliferation of cells in BM, blood, and other tissues
What are the two main classifications of leukemias?
- Acute: acute nonlymphocytic leukemias (ANLLs)
- Chronic: Myeloproliferative neoplasms
List diseases included the MPN category
- Chronic myeloid (or myelocytic) leukemia (CML)
- Chronic neutrophilic leukemia
- Polycythemia
- Chronic myelomonocytic leukemia
- Essential thrombocytopenia
- Primary myelofibrosis
- Chronic eosinophilic leukemia, not otherwise specified
- MPN, unclassifiable
List common traits of chronic MPNs
- Panhyperplasia of BM
- Extramedullary hematopoiesis
- BM fibrosis
- Overlapping manifestations btwn diseases
- Frequently end in acute leukemia
- Increased megakaryocytes in BM
- Platelet dysfunction
- Cytogenetic abnormalities
Traits of CML?
- Most common over 45 y/o
- Abnormal Philadelphia chromosome
- Rare eosinophilic and basophilic leukemia -> very acute
What is the Philadelphia chromosome (Ph22) abnormality?
Translocation (gene swap) between two chromosomes such that tyrosine kinase activity is increased. This leads to uncontrolled production of abnormal blood cells. Apoptosis lost
What are CML lab findings (there’s a lot, sorry!)?
- Left shift (blasts < 10%) bc Ph22 causes premature cells to be released)
- WBC 50,000-800,000/mm3 (blood resembles BM)
- ~90% are Ph22 positive
- Ph22 negative CML tend to have atypical disease, more acute, less responsive to chemo
- Reduced LAP
- Usually remarkable thrombocytosis
- Anemia (may see nRBCs)
- Increased basophils
- Hypercelullar BM, M:E is 10:1 to 50:1
- May see pseudo-Gaucher cells
List lab findings of CML-AP (accelerated phase)
- Blasts range 10%-19% in blood and/or BM
- Blood basophils >= 20%
- High WBC unresponsive to treatment
- Super high PLT unresponsive to treatment
- Very low PLT also possible, not caused by treatment
- Clonal cytogenetic abnormality
List lab findings for CML-BP (blast phase or blast crisis)
- Blasts >= 20% in blood and/or BM
- Transforms to AML (M2 usually) or ALL (lymphoblasts > 5%) or rarely others
- Myeloid sarcoma (**ICC: idk what this is someone please correct this info)
- 2-6 month life expectancy
How do you treat CML?
- BM transplant
- OHSU doc came up with drug to inhibit mutant tyrosine kinase -> prolongs chronic phase but blast crisis still happens
List lab findings for CNL (neutrophilic) with OR without CSF3R mutation
- Rare, avg 1.8 yr survival rate
- PMNs or bands >= 80% (no left shift)
- Hypercellular BM (M:E may be greater than 20:1)
- Neutrophilic leukocytosis persists without left shift evidence and absence of sepsis
- Toxic granules and Dohle bodies
- High LAP (350-400)
- Slightly reduced platelet
- Mild anemia
Differences between leukemoid reaction and CNL in terms of LAP score and left shift?
Leukemoid reaction: High LAP and left shift evident
CNL: High LAP but NO left shift apparent
Describe chronic monocytic leukemia
- New classification is chronic myelomonocytic leukemia (CMML)
- Myelodysplastic and MPN (see overlap between the two)
- If doesn’t meet criteria of CMML -> ID as clonal monocytosis of undetermined significance
Define polycythemia
Malignant increase in red cell mass (better indicator of how many RBCs there are) characterized by JAK2 mutation
List polycythemias
- Polycythemia vera/rubra vera
- Secondary polycythemia
- Relative erythrocytosis
List lab findings of polycythemia vera
- Hgb and/or Hct increase
- M Hgb > 16.5 g/dL, Hct > 49%
- F Hgb > 16.0 g/dL, Hct > 48 % - Initially, RBC’s look normal
- Hypercellular BM due to malignancies (too much erythropoiesis, myelopoesis, and megakaryopoiesis)
- Ineffective extramedullary hematopoiesis leads to increased aniso and poik as disease progresses
Describe JAK2 mutation
- Leads to endogenous erythroid colony formation (EEC), which means the body doesn’t need EPO to produce RBCs
- Body responds to mutation effects by decreasing EPO in attempt to shut down RBC production. This doesn’t matter tho bc malignant RBCs don’t need EPO to be made anyway
List more lab findings of polycythemia vera (didn’t want to put them all on same flash card cuz too clunky). Hint: about LAP and O2 saturation
- Increased granulocytes and platelets, so see high LAP
- Normal arterial O2 saturation
- Careful when drawing blue top tube bc increased RBC mass -> reduced plasma volume, which means too much sodium citrate in tube. Must do calc to remove anticoag (we’re not doing this yet)
- Hemostasis results may be affected by wrong anticoagulant to blood plasma ratio
Describe iron deficiency characteristics in polycythemia vera
- PLT hypofunction -> keep bleeding
- Repeated therapeutic phlebotomy (NOT lobotomy…I ‘m so tired I misread it that way)
- Increased RBC production and Fe turnover
- Reduced RBC survival (this is good bc limits expanding RBC mass. More RBC mass increases chance of thrombosis)
Describe RBC morphology in polycythemia vera
- Long-term PV leads to tear drop cells due to increasing myelofibrosis
- Become anemic bc body gets tired of putting in effort to make RBCS, so it just gives up. This is called spent phase aka post polycythemia myeloid metaplasia
Anemia with leukoerythroblastosis (immature RBC And WBC seen in peripheral blood) is seen in which disease state?
Myeloid metaplasia
What causes secondary polycythemia? Lab findings?
- Cause: Hypoxia (so it’s not malignant)
- Labs: Reduced arterial O2 saturation, increased EPO, Increased RBC mass due to more BM erythropoiesis, normal granulocytes and PLTS so normal LAP
What are the two most common groups that feature relative erythrocytosis?
- Dehydrated groups most common
- Asymptomatic middle-aged white males that are hypertensive, obese, and have long smoking history
Lab findings in relative erythrocytosis?
- Reduced plasma volume (leads to elevated Hct, but normal RBC mass due to reduced plasma volume)
- Normal O2 saturation
- Normal EPO, it just falsely appears like increased RBC production
- Normal LAP
Lab findings for essential thrombocytopenia (ET)?
- Increased BM megakaryopoiesis and slightly increased granulopoiesis
- PLT > 600,000/mm3
- Spontaneous PLT aggregation and function defects (thrombotic + hemorrhage complications)
- JAK2 gene mutation + EEC in 30-50% of pts
Describe what you see in blood smear in patients affected with ET
- Large masses of PLT aggregates
- Giant, bizarre PLTs
- Occ. megakaryocyte fragment
- Mild normocytic, normochromic anemia, unless Fe deficiency due to too much bleeding
- Neutrophilia, occ increased eos and basos
Describe WBC, PLT, and RBC findings in early primary myelofibrosis (PMF)
- WBCs and PLTs may be increased, normal, or decreased
- May see increased basos + eos
- Immature granulocytes + pseudo Pelger-Huet
- Micromegakaryocytes
- May have abnormal PLT shape and impaired function (leads to too much bleeding)
- RBCs: anemia with nRBCs, polychromatic, and bizarre shapes
- Hallmark of disease = teardrops
Describe general presentation of primary myelofibrosis (PMF)
- Can present de novo or progression of PV or ET
- Most have JAK2, CALR, or MPL mutation -> higher CD34+ count -> correlates to progression to marrow fibrosis
- Clonal cells stimulate release of fibroblastic growth factor
- BM dry tap common so do biopsy for best luck
Describe PMF presentation once disease progresses to more serious form
- Ineffective erythropoiesis + hemolysis
- Extramedullary hematopoiesis, so see more nRBCs and poik
- Reduced WBC and PLT (see immature granulocytes, megakaryocytic fragments, and microplatelets)
Describe Chronic eosinophilic leukemia not otherwise specified (CEL NOS)
- Eosinophilia with no signs of allergy, parasitic infections, or other malignancies associated with this
- Myeloblasts: may be elevated in BM but less than 20%
- Eosinophils infiltrate tissues and organs leading to organ dysfunction
List other MPNs
- iHES (idiopathic hypereosinophilic syndrome)
- M/LN-eo (myeloid lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions
- Systemic mastocytosis
- MPN-U (MPN, unclassifiable)
