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MPD Flashcards

1
Q

CHRONIC MYELOPROLIFERATIVE DISORDERS: Recognized by WHO

A

1) Chronic Myeloid Leukemia
2) Chronic Neutrophilic Leukemia
3) Polycythemia vera
4) Primary myelofibrosis
5) Essential thrombocythemia
6) MPN with eosinophilia (and abnormalities of PDGFRA, PDGFRB, FGFRI)
7) Chronic eosinophilic leukemia
8) Mastocytosis
9) Myeloproliferative neoplasm, unclassifiable

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2
Q

Middle-aged (25-40 yrs old)

A

CHRONIC MYELOLOGENOUS LEUKEMIA (CML)

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3
Q

BCR-ABL present

A

CHRONIC MYELOLOGENOUS LEUKEMIA (CML)

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4
Q

t(9:22)(q34;q11) BCR-ABL1

A

CHRONIC MYELOLOGENOUS LEUKEMIA (CML)

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5
Q

Dependent on response to TKI

A

CHRONIC MYELOLOGENOUS LEUKEMIA (CML)

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6
Q

Older adults (>40 yrs old)

A

CHRONIC NEUTROPHILIC LEUKEMIA (CNL)

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7
Q

Neutrophilia > 2,000/uL

A

CHRONIC NEUTROPHILIC LEUKEMIA (CNL)

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8
Q

CSF3R mutation

A

CHRONIC NEUTROPHILIC LEUKEMIA (CNL)

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9
Q

Indolent

A

CHRONIC NEUTROPHILIC LEUKEMIA (CNL)

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10
Q

Middleaged, M > F (25 to early 40s)

A

POLYCYTHEMIA VERA (PV)

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11
Q

Major criteria: Hb >18.5 g/dL in M or >16.5 g/dL; mutation in JAK2 V617F
 confirmatory

A

POLYCYTHEMIA VERA (PV)

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12
Q

Minor criteria: hypercellular marrow with panmyelosis; ↓EPO; ↑endogenous erythroid colony formation in vitro; 2 major plus 1 minor, or first major plus 2 minor criteria

A

POLYCYTHEMIA VERA (PV)

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13
Q

JAK2 V617F, negative t(9;22)

A

POLYCYTHEMIA VERA (PV)

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14
Q

10-20 years

A

POLYCYTHEMIA VERA (PV)

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15
Q

> 50 years

A

PRIMARY MYELOFIBROSIS (PMF)

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16
Q

Major criteria: megakaryocyte proliferation/atypia with marrow fibrosis; CML, PV, MDS ruled out; JAK2 V617F

A

PRIMARY MYELOFIBROSIS (PMF)

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17
Q

 CML, PV: thrombocytosis
 CML: BCR-ABL
 PV: inc rbc
 MDS: dysplastic megakaryocyte lineage

A

PRIMARY MYELOFIBROSIS (PMF)

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18
Q

Minor criteria: leukoerythroblastosis, ↑LD, anemia, splenomegaly; all 3 major plus 2 minor criteria

A

PRIMARY MYELOFIBROSIS (PMF)

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19
Q

+8, +9, del(20q), del(13q), del(1p), negative t(9;22)

A

PRIMARY MYELOFIBROSIS (PMF)

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20
Q

Dependent on phase: ≈10 years in early prefibrotic phase (infiltration of cells); ≈5 years in fibrotic phase; 10-15 years before death

A

PRIMARY MYELOFIBROSIS (PMF)

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21
Q

→ Poikilocyte: Tear-drop cell

A

POLYCYTHEMIA VERA (PV)
PRIMARY MYELOFIBROSIS (PMF)

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22
Q

5th decade/5 mos old (M = F), second peak in 30s (F > M)

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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23
Q

Platelet count >450,000 (N: 200, 000-400,000); BM with proliferation of mature megakaryocytes; PV, PMF, CML, MDS ruled out; JAK2 V617F

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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24
Q

CML: proliferation of granulocytes
PMF: myelofibrosis
PV: inc rbc

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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25
Q

NOTE: All four criteria must be met.

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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26
Q

JAK2 V617F in 50%

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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27
Q

del(13q22), +8, +9 seen in 5%-10% of cases

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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28
Q

negative t(9;22)

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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29
Q

Stable for many years (most cases)

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

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30
Q

→ May have symptoms of anemia and rapid weight loss

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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31
Q

→ May complain of malaise (night sweats)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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32
Q

 due to high wbc/granulocyte turn over (1 hour instead of <20 days)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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33
Q

→ Spleen enlarges progressively resulting to high fever and night sweats (Splenomegaly)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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34
Q

 due to high fever and night sweats

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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35
Q

→ (Latent) Excessive bleeding or bruising

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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36
Q

 internal bleeding and abnormal coagulation

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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37
Q

→ Lymphadenopathy

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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38
Q

 swollen lymph glands; enlargement of lymph nodes due to viral infection

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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39
Q

 prone to mild-severe infections

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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40
Q

→ WBC ct: over 5x109/L (may exceed 30x109/L)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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41
Q

 normal: 4-11x109/L

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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42
Q

 Neutrophil peak (makes up 70% of wbc)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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43
Q

 Present: Basophilia and Eosinophilia, and Increased Monocytes

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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44
Q

 Absent: Llymphocytes → anemia is present

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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45
Q

 Normocytic anemia: normal shape, size and color, but few

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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46
Q

 Thrombocytosis is very common

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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47
Q

→ Marrow: Markedly hypercellular

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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48
Q

 viscous blood (same ass dehydration) = difficulty in aspiration of bm = bm biopsy o due to reticulin

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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49
Q

 hypercellularity is due to dense cell and increased reticulin

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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50
Q

 exhibits Macrophages Laden/Sea-blue histiocytes appearance (normally: light)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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51
Q

→ NAP (Neutrophil Alkaline Phosphatase): reduced or absent

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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52
Q

 Enzyme found in neutrophils

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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53
Q

 Not seen in CML due to dysmyelopoiesis (abnormal neut prod)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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54
Q

 ↑wbc turn over rate, proliferation of neutrophil, basophil, eosinophil = abnormal wbc = genetic problem in the production of granulocytes

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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55
Q

 Hallmark of CML

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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56
Q

→ Cytogenetic abnormalities: Ph chromosome (Philadelphia)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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57
Q

 abnormal type of chromosome present in px w/ CML

A

Ph chromosome (Philadelphia)

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58
Q

 Cause: mutation of both ABL-1 gene of Ch 9 and BCR gene of Ch 22

A

Ph chromosome (Philadelphia)

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59
Q

abnormal chromosome containing the abnormal gene

A

Ph chromosome (Philadelphia)

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60
Q

: abnormal gene

A

 BCR-ABL gene

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61
Q

 Etiolgy:

A

from Ch 9 and Ch 22 abnormalities

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62
Q

→ Prognosis: TKl targets BCR-ABL and results in long term remissions.

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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63
Q

 Dependent of response to TKI (cytokine supressed targeting BCR-ABL gene; appearance causes long-term remission of CML)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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64
Q

 in chemotherapy, TKI is supressed to supress the mutation on Ch 9 and Ch 22

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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65
Q

→ Progression: aggressive; marrow blast increases from 10% to 19%, >20% basophilia, thrombocytosis >100, leukocytosis and splenomegaly, dysplasia of megakaryocytes and reticulin fibrosis

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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66
Q

 From 10% blasts to 19%

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
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67
Q

: progression to AML (short month-lifespan)

A

> 20% blast
70% of T and B lineage

68
Q

 >20% of persistent basophilia

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
69
Q

 Thrombocytosis: >1 million (normal: 200-450)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
70
Q

 Splenomegaly

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
71
Q

 Reticulin fibrosis: abnormal prod of reticulin causing fibrotic bm

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
72
Q

 70% of T and B lineage appears

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
73
Q

Lymphocyte does not appear in the circulation

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
74
Q

→ Blast phase progresses to AML (>20% blast in blood or BM, aggregates extramedullary, myeloid lineage encompasses 70% of cells, occasionally B and T lineage appears)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
75
Q

Serum cobalamin and transcobalamin: increased

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
76
Q

is required for normal segmentation of wbc

A

Vit B12 (cobalamin)

77
Q

Inc prod of granulocytes

A

Serum cobalamin and transcobalamin

78
Q

 Serum muramidase (lysozyme): increased

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
79
Q

Enzyme found in granulocytes

A

Serum muramidase

80
Q

 Ph Ch positive (w/ neutrophilia)

A
  1. CHRONIC MYELOLOGENOUS LEUKEMIA (CML)
81
Q

→ Persistent and unexplained (no cause) neutrophilia (>25x109/L) and mature granulocytes

82
Q

 Normally happens w/ bacterial infection

83
Q

 No infection that preceded the disease

84
Q

→ Resembles: reactive neutrophilia

85
Q

 Infection: wbc reacts with microorganism

86
Q

→ Associated conditions:
a. Splenomegaly
b. Hepatomegaly
c. Mucocutaneous bleeding

87
Q

: liver becomes overworked in the production of proteins needed in neutrophil production

A

b. Hepatomegaly

88
Q

: components under the skin (outside the bv) does not normally interact w/ neutrophil; causes appearance of pus

A

c. Mucocutaneous bleeding

89
Q

: inflammation of the joint

A

Pruritis/gout

90
Q

→ Left shift with bands and toxic granulation

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
91
Q

→ BM findings: Hypercellularity with granulocytes (neutrophil)

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
92
Q

 M:E → 20:1
Normal M:E → 3 wbc : 1 rbc

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
93
Q

Due to hyperplastic granulocytic lineage

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
94
Q

*Predominance of mature neutrophils to myelocytes.

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
95
Q

→ Cytogenetic abnormalities: includes +8, +9, del (20q) and del (11q)

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
96
Q

 Hyperplasia (not dysplasia)

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
97
Q

 Mutation on CSF3R gene

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
98
Q

→ Prognosis: Indolent

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
99
Q

 progressing slowly; not life threatening
 does not progress to AML

A
  1. CHRONIC NEUTROPHILIC LEUKEMIA (CNL)
100
Q

→ Affects erythroid lineage

A
  1. POLYCYTHEMIA VERA (PV)
101
Q

 increased RBC; abnormal proliferation

A
  1. POLYCYTHEMIA VERA (PV)
102
Q

→ Panmyelosis

A
  1. POLYCYTHEMIA VERA (PV)
103
Q

 increase in all bone marrow cell (wbc, megakaryocyte)

A
  1. POLYCYTHEMIA VERA (PV)
104
Q

 increased only (not marked or pronounced)

A
  1. POLYCYTHEMIA VERA (PV)
105
Q

→ Absolute increase in red cell mass, leukocytosis and thrombocytosis

A
  1. POLYCYTHEMIA VERA (PV)
106
Q

 ESR increased

A
  1. POLYCYTHEMIA VERA (PV)
107
Q

→ Serum and urine EPO is DECREASED or NORMAL

A
  1. POLYCYTHEMIA VERA (PV)
108
Q

 Will not cause stimulation but proliferation of red cell in the bm

A
  1. POLYCYTHEMIA VERA (PV)
109
Q

→ Proliferation of erythrocytes is autonomous with EECs (endogenous erythroid colonies)

A
  1. POLYCYTHEMIA VERA (PV)
110
Q

 Abnormal cells in the bm that produces rbc w/o stimulation from EPO

A
  1. POLYCYTHEMIA VERA (PV)
111
Q

 increased causing proliferation of rbc w/o EPO

A
  1. POLYCYTHEMIA VERA (PV)
112
Q

→ Frequency: men

A
  1. POLYCYTHEMIA VERA (PV)
113
Q

→ Cyanosis is present

A
  1. POLYCYTHEMIA VERA (PV)
114
Q

 Bluish/pale discoloration of the skin

A
  1. POLYCYTHEMIA VERA (PV)
115
Q

 Red cells cannot deliver oxygen since they are very saturated in the circulation = very viscous blood

A
  1. POLYCYTHEMIA VERA (PV)
116
Q

→ Splenomegaly is present

A
  1. POLYCYTHEMIA VERA (PV)
117
Q

 Accommodates extra red cells in the circulation instead of platelet

A
  1. POLYCYTHEMIA VERA (PV)
118
Q

→ Thrombosis is most common
 Due to inc cells in the bm

A
  1. POLYCYTHEMIA VERA (PV)
119
Q

→ GIT bleeding is common as well as Pruritus

A
  1. POLYCYTHEMIA VERA (PV)
120
Q

 Joint cavity is inflamed (accumulation of rbc in the joints)

121
Q

 Aka Gout

122
Q

→ RBC count: >6-10x1012/L

A
  1. POLYCYTHEMIA VERA (PV)
123
Q

→ Hemoglobin: >18.5 (M) ; >16.5 (F)

A
  1. POLYCYTHEMIA VERA (PV)
124
Q

→ Hypochromic and microcytic if chronic blood loss has occurred

A
  1. POLYCYTHEMIA VERA (PV)
125
Q

 Iron is depleted

A
  1. POLYCYTHEMIA VERA (PV)
126
Q

→ Production: increased

A
  1. POLYCYTHEMIA VERA (PV)
127
Q

→ Destruction: decreased

A
  1. POLYCYTHEMIA VERA (PV)
128
Q

 Accumulation of rbc in the circulation

A
  1. POLYCYTHEMIA VERA (PV)
129
Q

→ Upon progression: splenomegaly (chronic; after 1year of the disease); decreased survival (macrophages in the spleen destroys rbc)

A
  1. POLYCYTHEMIA VERA (PV)
130
Q

→ Blood volume: increased

A
  1. POLYCYTHEMIA VERA (PV)
131
Q

→ ESR: increased

A
  1. POLYCYTHEMIA VERA (PV)
132
Q

→ PIatelet count: 1000x109/L

A
  1. POLYCYTHEMIA VERA (PV)
133
Q

→ WBC: neutrophilic leukocytosis with immature granulocyte

A
  1. POLYCYTHEMIA VERA (PV)
134
Q

→ Hyperuricemia is common with increased nucleic acid metabolism

A
  1. POLYCYTHEMIA VERA (PV)
135
Q

 Due to increased uric acid from increased DNA and RNA metabolism (protein is broken down = NA, RNA, DNA = waste product: uric acid → liver & kidneys to be excreted ≠ returns to the circulation = accumulation of uric acid in the joints = gout)

A
  1. POLYCYTHEMIA VERA (PV)
136
Q

 inc rbc = inc retic = inc RNA remnants (accumulated to waste prods)

A
  1. POLYCYTHEMIA VERA (PV)
137
Q

→ BM: moderate-to-markedly hypercellular with prominent normoblastic erythroid hyperplasia and panmyelosis

A
  1. POLYCYTHEMIA VERA (PV)
138
Q

→ lncreased reticulin (makes the blood viscous; present in the bm)

A
  1. POLYCYTHEMIA VERA (PV)
139
Q

→ Storage iron is decreased to absent

A
  1. POLYCYTHEMIA VERA (PV)
140
Q

→ Major criteria for diagnosis:
1) Hemoglobin
2) Presence of mutation (JAK12, exon 12)

A
  1. POLYCYTHEMIA VERA (PV)
141
Q

→ Prognosis: 10–20 years

A
  1. POLYCYTHEMIA VERA (PV)
142
Q

→ Progression: Anemia (chance: 20-40%)

A
  1. POLYCYTHEMIA VERA (PV)
143
Q

 proliferation of rbc = decreased survival

A
  1. POLYCYTHEMIA VERA (PV)
144
Q

 CML & CNL → AML ; PV → Anemia

A
  1. POLYCYTHEMIA VERA (PV)
145
Q

 normal response to blood loss (inc in plt = blood clot : first responder in coagulation)

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

146
Q

 requires a lot of plt = inc plt = reactive thrombocytosis (blood loss/excessive bleeding)

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

147
Q

 abnormal increase of plt w/o stimulation of TBO

A

ESSENTIAL/PRIMARY THROMBOCYTOSIS (ET)

148
Q

▪ disorders that show features of both myelodysplastic and myeloproliferative disorders

A

MYELODYSPLSTIC/MYELOPROLIFERATIVE DISORDERS

149
Q

▪ characterized by increases in cells as well as cytopenia and morphologic dysplasia

A

MYELODYSPLSTIC/MYELOPROLIFERATIVE DISORDERS

150
Q

MYELODYSPLSTIC/MYELOPROLIFERATIVE DISORDERS:

151
Q

Normal:

A

CML starts w/ dysplastic refractory cytopenia due to inc apoptosis (supressed in late stages of MDS) = proliferation of abnormal neutrophil → CNL → Lekukemia

152
Q

• persistent monocytosis of > 1 x 109 /L for more than 3 months

A
  1. CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
153
Q

• with 20% blasts and promonocytes in the PB and BM

A
  1. CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
154
Q

• with dysplasia in one or more myeloid cell line

A
  1. CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
155
Q

• positive (+): - alpha naphthyl acetate, alpha naphthyl butyrate esterase

→ monocytes usually react with both stains

A
  1. CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
156
Q
  • < 5% blasts and promonocytes in the PB
157
Q
  • < 10% in the BM
158
Q

(more severe):

159
Q
  • 5%-19% blasts and promonocytes in the PB
160
Q
  • 10%-19% in the BM
161
Q

▪ characterized by leukocytosis (↑mature and immature neutrophils) with prominent dysgranulopoiesis (abnormal/defective structure production of WBCs)

A
  1. ATYPICAL CHRONIC MYELOID LEUKEMIA (ACML), BCR-ABL1 NEGATIVE
162
Q

▪ BCR-ABL1 negative

A
  1. ATYPICAL CHRONIC MYELOID LEUKEMIA (ACML), BCR-ABL1 NEGATIVE
163
Q

▪ predominantly granulocytic (BEN) and monocytic lineages

A
  1. JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)
164
Q

Ph negative CML

A
  1. JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)
165
Q

Monosomy 7

A
  1. JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)

Hematology 2 Lec (29 decks)

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