Term
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Definition
• Presentation – can be asymptomatic, or have constitutional Sx, weight loss, HSM, bruising, leukostasis
o Weight loss – due to increased cells & thus increased metabolism
o Leukostasis – rare; overproduction of cells leads to pulmonary/neurologic Sx, priapism due to thrombi |
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Term
| Diagnosis: Labs, palpation, cytogenetic... |
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Definition
• Dx – based on leukocytosis with left shift, hypercellular marrow, increased M:E ratio, mild anemia and eosino/basophilia
o Splenomegaly – also diagnostic feature, as spleen fills up with cells
o QUIZ: Philadelphia chromosome – common feature of many CML patients 9-22 translocation (necessary and sufficient)
BCR/ABL gene – codes for hybrid protein causing CML, due to 9-22 translocation
BCR/ABL amplication – can be done through RNA PCR detect hybrid gene
Fluoresence – can fluorescent tag BCR/ABL gene, and fluorescence ~ protein load
High load – high amounts of BCR/ABL gene = more severe CML |
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Term
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Definition
| • Pathophysiology – protein kinase coded by bcr-abl fusion alters all cell functions proliferation/transformation, anti-apoptosis, proliferation and adhesion |
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Term
| Best methods of testing for it? |
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Definition
• Testing (PCR = most sensitive, cytogenetics = least sensitive)
o Cytogenetics – looks for Ph chromosome, confirms dx, evaluates for other abnormalities (clonal evolution)
o FISH – looks for juxtaposition of bcr and abl; confirms dx, monitor therapeutic response Red9+Green22 => Yellow
o RT-PCR – amplify bcl-abl mRNA; can detect breakpoints of fusion gene, most sensitive and allows quantitative! |
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Term
CML vs. MDS?
CMS vs. reactive leukocytosis? |
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Definition
• Vs. MDS – CML has hyperproliferation of normal cell lines, whereas MDS has dysplastic
• Vs. Leukemoid Reaction (Reactive leukocytosis) – elevated leukocytes in blood due to stimulus
o Leukocyte alkaline phosphatase – has a high level in reactive leukocytosis, low in CML
o Non-basophilic – leukemoid doesn’t show basophilia; CML has basophilia |
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Term
| CML Stages? Chronic, accelerated, blast crisis |
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Definition
• Chronic Phase – usually minimal symptoms
• Accelerated Phase – 10-19% blasts, progressive anemia/thrombocytopenia/thrombocytosis, clonal evolution (additional genetic abnormalities not present at time of chronic phase dx)
• Blast Crisis – >20% of blasts in blood/marrow, often refractory to treatment, large foci of blasts in bone marrow
• Treatment goals – prevent progression to blast crisis |
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Term
| Polycythemia - def, relative vs. true |
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Definition
• Polycythemia (erythrocytosis) – an elevated RBC concentration in the blood, categorized as: hi hct or hgb production…
o Relative polycythemia – elevated concentration due to decreased plasma volume (dehydration)
o True polycytehmia – elevated concentration due to excess RBCs
Polycythemia vera – a specific type of true polycythemia which is EPO-independent |
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Term
| • True Polycythemia Etiology |
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Definition
– due to primary or reactive EPO excess, or Epo independent:
o Hypoxia, carboxyhemoglobinemia, Cushing’s, EPO secreting tumors (renal cell ca.)
o Epo-independent true polycythemia – polycythemia vera |
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Term
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Definition
| anemia, JAK2V617F mutation (95%), marrow trillineage expansion, subnormal EPO, endogenous erythroid colony growth |
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Term
| role of JAK2 & Polycythemia Vera |
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Definition
• JAK2 – a tyrosine kinase mutated in polycythemia vera & other myeloproliferative disorders
o Function – relays signal of Epo-binding receptor outside HSC into cell, signaling proliferation
o JAK2 Mutation – a gain-of-function mutation will activate JAK2 regardless of Epo binding; V617F substitution
o Chromosome 9p – site of gene mutation, these are ACQUIRED…genetic mutation ONLY in bone marrow!
• JAK2 Dx – not perfect diagnostic marker, not found in all PCV patients, although common mutation
• Therapeutic Target – currently developing therapies targeting JAK2 kinase |
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Term
| presentation of PV patient |
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Definition
• Presentation – high RBC count manifests as ruddy complexion, conjunctival plethora, thick blood:
o Blood hyperviscosity – neurologic (& resp?) symptoms headache, vertigo, confusion
o Thrombotic Risk – characteristic of PCV CVA, MI, DVT, ischemia
o Occult GI bleeding – presents with Fe deficiency |
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Term
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Definition
goal is to lower RBC in order to reduce thrombosis risk:
o Phlebotomy – remove a chunk of RBCs from blood through a bleed
o Hydroxyurea – chemotherapeutic agent causing RBC destruction for high risk pts (>70, prior thrombosis, platelets > 1.5mm, CV risk factors) |
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Term
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Definition
• DDx – most commonly 2o to other causes, otherwise related to myeloproliferative disorders, or essential:
o Compensatory to Cause – acute hemorrhage response, bone marrow recovery
o Other Causes – malignancy, asplenia, Fe deficiency anemia, drug-induced
o Myeloproliferative disorder – makes for viscous blood, coagulability risk
o Essential thrombocytosis – diagnosis of exclusion |
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Term
| • Essential Thrombocytosis Presentation |
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Definition
o Vasomotor symptoms – HA, syncope, atypical chest pain, acral paresthesia, livedo reticularis, erythromelalgia
o Thrombosis and hemorrhage
o Early satiety – abdominal bloating due splenomegaly
o JAK2V617F – present in 50% of pateients |
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Term
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Definition
o Platelet count > 450k
o Megakaryocytic proliferation – large, mature morphology
o Rule out – CML, PV, PMF, MDS or other neoplasm
o Clonal marker – JAK2V617F or other marker or lack of evidence of a secondary marker |
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Term
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Definition
o Normal life expectancy – most patients
o Thrombosis – major risk if over 60, prior thrombosis, long term plt count > 1mm
o Transformation – to myelofibrosis or AML |
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Term
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Definition
low risk, give ASA; attempt to lower platelet count if high risk:
o Hydroxyurea, INFα – chemotherapeutics lowering platelet count
o Anagrelide – interferes with megakaryocyte development lowers platelet count but assoc w/ increased risk of vascular events |
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Term
Sx and presentation of px: • S/Sx – can be asymptomatic, but most have symptoms: fatigue, hepato/splenomegaly, fever/night sweats, anemia, thrombocytopenia, foci of extramedullary hematopoiesis outside of BM that’s not effective, bone or joint involvement.
• CBC – anemia, ansiopoikilocytosis, teardrop RBCs, nuc RBCs, leukoerythroblastosis, variable WBC and plt counts
What's the diagnosis? |
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Definition
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Term
| BM biopsy in primary myelofibrosis shows: |
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Definition
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Term
| Primary Myelofibrosis Prognosis – |
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Definition
| cytopenias worsen as fibrosis progresses; rare transformation to acute leukemia |
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Term
| JAK2 V617F is there 100% of the time in Primary myelofibrosis? |
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Definition
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Term
| Tx for primary myelofibrosis: |
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Definition
asymptomatic can just manage
o Symptomatic – hydroxyurea, androgens, corticosteroids, splenectomy, splenic irradiation, thalidomide/lenalidomide
o High risk and < 55 – reduced intensity allogeneic BMT
o Only curative => TRANSPLANT…the worse the blood counts/Sx, worse the outcome |
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Term
| PCR is sufficient to diagnose the BCR-ABL gene/translocation |
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Definition
| False: PCR can be negative b/c of minor differences in break points leading to unusual gene product so in those cases you have to use FISH as the diagnostic tool! |
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