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BL and DD Unit 3 > BL > Flashcards

BL Flashcards

1
Q

What is acute leukemia?

A
  • Acute leukemia is a clonal, neoplastic proliferation of immature myeloid or lymphoid cells (two types as a result: AML and ALL) - Acute means it is rapidly fatal without treatment
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2
Q

How does acute leukemia work?

A

Immature leukemic cells that do not mature past a blast or other precursor stage accumulate in bone marrow and cause bone marrow dysfunction and there for loss of peripheral blood cells

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3
Q

What is the etiology of AML?

A

Chromosomal abnormalities affecting oncogenes, TS, or regulation of apoptosis lead to inability for cells to mature/differentiate and for them not to be regulated by external factors for growth and also inexhaustibly self-renews For AML, genetic disturbance at myeloid precursor –> AML types affecting myeloid lineages (granulocytes, monocytes, eythrocytes, megakaryocytes)

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4
Q

What is the etiology of ALL?

A

Similar to AML, but defect in lymphoid stem cell –> either B cell or T cell affected, but these cells don’t fully mature 75% of ALL cases occur in kids

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5
Q

What are risk factors for acute leukemia?

A

Chemotherapy (especially DNA alkylating agents and topoisomerase II inhibitors), smoking, ionizing radiation, benzene, other genetic syndromes (Down, Bloom, Fanconi anemia, ataxia-telangiectasia)

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6
Q

What are the signs and symptoms of acute leukemia?

A

Same things related to cytopenia: anemia (fatigue, dyspnea), thrombocytopenia (bruising, hemorrhage) neutropenia (fever/infection) However, sometimes present due to leukemic cells: thrombosis due to inc. WBC –> inc. blood viscosity, DIC initiated by WBCs, and can infiltrate mucouse membranes

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7
Q

What expresses CD34?

A

Immature lymphoblasts and myeloblasts

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8
Q

What expresses TdT?

A

Only lymphoblasts (no myeloblasts and no lymphocytes)

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9
Q

What do B-lymphoblasts express?

A

CD19, CD22, and/or CD79a, but not CD20 or surface Ig

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10
Q

Describe the cytogenetics of BALL

A

1) t(9:22)(q34;q11.2); BCR-ABL1 [Philadelphia chromosome] - 25% of adult cases (2% of child) - worst prognosis 2) 11q23; MLL - neonates/young infants - poor prognosis 3) t(12:21)(p13;q22); ETV6-RUNX1 - 23% of childhood BALL - very favorable prognosis

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11
Q

Describe T-ALL

A

Only 25-30% of ALL cases In adolescents/young adults primarily Presents more commonly with LBL with masses More likely to present with high WBC Males>females

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12
Q

What do T-lymphoblasts express?

A

CD2, CD3, and/or CD7; also CD4, CD8; also CD99, CD1a

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13
Q

What are other prognostic factors for ALL aside from cytogenetic findings?

A

Worse prognosis for 10yo/adults Worse if WBC is elevated Worse if hypodiploidy Worse if T-ALL

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14
Q

What is the diagnostic criteria for AML?

A

Either myeloblasts accounting for >20% of nucleated cells in the marrow/peripheral blood (detected through smears, flow cytometry, or immunohistochemistry on marrow biopsy) OR one of the genetic mutations

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15
Q

What do immature myeloblasts express?

A

CD34 (but also on lymphoblasts), CD117, myeloperoxidase, For monocytic diff –> CD64, CD14 For megakaryoblastic diff –> CD41, CD61 Also contain Auer rods (which help to distinguish from lymphoblasts)

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16
Q

Describe the cytogenetics of AML

A

Typically balanced translocations 1) t(8;21)(q22;q22); RUNX1-RUNX1T1 - 5% of cases - AML w/ maturation (some neutrophil production) - blocked transcription of CBF-dep genes –> blocked differentiation - good prognosis 2) inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 - 5-10% of cases - lots of immature eosinophils with abnormal basophilic granules (baso eos) - inc. myeloblasts and monocytes (myelomonocytic leukemia) - similar to CBF in (1) - good prognosis *3) t(15;17)(q22;q12);PML-RARA - **important** - promyelocytes instead of blasts - 5-10% of cases - hypergranular (normal promyelocytes with lots of granules, Auer rods) - retinoic acid receptor alpha (RARA) needed for promyelocytes to deveop, but can overcome by giving retinoic acid - can cause DIC 4) t(1;22)(p13;q13);RBM15-MKL1 - megakaryoblastic diff - seen in infants w/ Down syndrome - good prognosis w/ chemo 5) 11q23; MLL - monocytic diff - poor prognosis

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17
Q

Describe the differences between therapy related AML secondary to alkylating agents/radiation and topoisomerase II inhibitors

A

AA/radiation - 2-8yrs of latency - goes through MDS before AML - whole or partial loss from chromosome 5 and/or 7 topoisomerase II inh - 1-2 years of latency - de novo AML skipping MDS - rearrangement of MLL gene (11q23) both have poor prognoses

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18
Q

What if there are no cytogenetic findings?

A

Then called AML, NOS (not otherwise specified) and you look at differentiation of leukemic cells: - myeloid if myeloblasts - myelomonocytic if myeloblasts and monoblasts/monocytes - monoblastic/monocytic if monoblasts and monocytes (may infiltrate skin) - eyrthroid if myeloblasts but erythroid precursors are inc - megakaryblastic - if megakaryoblasts/cytes and have marrow fibrosis However, are finding some genetic abnormalities: - FLT3 ITD: poor prognosis - NPM1 - good prognosis - CEBPA - good prognosis

19
Q

What about overall prognosis?

A

If poor prognosis, then 10years 60% of AML will go into remission after chemo Stem cell transplant is preferred treatment

20
Q

What two factors characterize MDS?

A

Ineffective hematopoiesis and increased risk of transformation to AML (basically similar to AML)

21
Q

How do you diagnose MDS?

A

Look for 2+ cytopenias: anemia, thrombocytopeia, or neutropenia Look at marrow - >10% of cells should show dysplastic changes - dyserythropoiesis - RBC precurosors with moth-eaten and/or multi-lobed nuclei, sideroblastic - dysgranulopoiesis - moth eaten bi-lobed (Pelger-Huet) nuclei, abnormally pale (instead of pink) cytoplasm due to lack of granules - dysmegakaryopoiesis - small and single lobed nuclei Look at cytogenetics - partial or whole deletions of chr 5 and/or 7, deletion 7q, deletion 5q, trisomy 8

22
Q

If no cytogenetics or increased myeloblasts and only dysplasia, then what?

A

Then need to exclude findings due to: - chemo - B12/folate def - viral infection - toxins

23
Q

What is low and high grade MDS?

A

Low grade: 5% and/or >2%

24
Q

What are the types of low grade MDS?

A

Refractory cytopenia with unilineage dysplasia - good prognosis - low grade MDS with dysplasia in only one lineage (usually anemia) Refractory cytopenia multilineage dysplasia - worse prognosis - 2+ lineages MDS w/ isolated deletion 5q - anemia, inc platelets, megakar with small, round, non lobed nuclei

25
Q

What are the high grade MDS?

A

Refractory anemia w/ excess blasts 1 - 5-9% blasts in marrow or 2-4% in peripheral blood RAEB2 - 10-19% in marrow, 5-19% in peripheral blood bad prognosis

26
Q

Why do MPNs present with hepatosplenomegaly?

A

because of the sequestration of excess blood cells and extramedullary hematopoiesis

27
Q

What can happen in MPNs if not treated?

A

can transform to AML can transform to MDS can have marrow fibrosis

28
Q

What are the 4 types of MPNs?

A

Chronic myelogenous leukemia (CML) Polycythemia vera (PV) Primary myelofibrosis (PMF) Essential thrombocythemia (ET)

29
Q

What are the initial symptoms of CML?

A

Fatigue, weight loss, night sweats, splenomegaly, anemia But can be asympotmatic and diagnosed by CBC indicating inc neutrophil

30
Q

Describe the progression of CML

A

Starts in chronic phase - blasts not elevated - neutrophils elevated - basophils and platelets are often increased - hypercellular due to granulocytic hyperplasia - small, round, non-lobed nuclei megakaryocytes - no dysplasia If not treated, moves to blast phase - basically AML (>20% blasts in marrow/blood) - blasts usually myeloblasts (70%) or lymphoblasts (30%)

31
Q

Describe the cytogenetics of CML

A

BCR-ABL1 gene fusion t(9;22)9q34;q11.2) - Philadelphia chromosome Results in 210 kD fusion protein as opposed to 190 kD in BALL

32
Q

How do you treat and diagnose CML?

A

Diagnose with karyotype or FISH and look for BCR-ABL PTKIs (protein tyrosine kinase inhibitors) - Gleevec;

33
Q

What is polycythemia vera characterized by?

A

Increase in RBC mass and inc neutrophils and plateleys (trilineage hyperplasia) Large, weird megakaryocytes Mutation of JAK2 gene with V617F point mutation

34
Q

If the JAK2 mutation isn’t found in PV, what could it be?

A

If persistent erythrocytosis, then maybe secondary erythrocytosis seen in smokers and chronic hypoxia

35
Q

Describe the progression of PV

A

Starts in a polycythemic phase with inc peripheral blood Progresses to spent phase where marrow fibrosis and peripheral blood dec and becomes similar to PMF

36
Q

What other symptoms are associated with PV?

A

Symptoms include headache, dizziness, visual problems, paresthesias, plethora, itching, splenomegaly (70%), and hepatomegaly (40%) Thrombosis of mesenteric, portal, or splenic vein

37
Q

How do you treat PV?

A

Good prognosis Phlebotomy (bloodletting) with aspirin to prevent clots Mild chemo

38
Q

What is PMF characterized by?

A

Proliferation of granulocytic and megakaryocytic lineages –> progressing to myelofibrosis (similar to PV but no erythrocytosis) JAK2 mutations in 50% of cases

39
Q

What is the course of PMF?

A

In prefibrotic stage: - hypercellular marrow with granulocytes and megakaryocytes - Megakaryocytes are large and weird and clustered - Thrombocytosis in blood and sometimes neutrophilia Progresses to fibrotic stage: - reticulin (type 4 collagen) fibrosis in marrow –> hematopoiesis in marrow sinusoids - leukoerythrobastosis - inc immature granulocytes and nuc RBCs and dacrocytes - splenomegaly

40
Q

How do you treat PMF?

A

Not diagnosed until fibrotic stage usually, so not that good of prognosis

41
Q

What is ET characterized by?

A

Sustained marked thrombocytosis No granulocytic hyperplasia in marrow Clustered large weird megakaryocytes in marrow JAK2 mutations in 50%

42
Q

What are the symptoms of ET?

A

Transient ischemic attacks due to occlusion of small blood vessels Digital ischemia with paresthesia Thrombosis of majore arteries and veins

43
Q

What is the prognosis of ET?

A

Symptom free for long periods, with occasional severe thrombotic of hemorrhagic events

44
Q

Describe the anatomy of lymph nodes

A

BL and DD Unit 3 (11 decks)

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