Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Clinical Haematology > Chapter 15: Myeloproliferative Neoplasms > Flashcards

Chapter 15: Myeloproliferative Neoplasms Flashcards

1
Q

What does the term myeloproliferative neoplasms mean?

A

The term myeloproliferative neoplasms (MPN) describes a group of conditions arising from transformed marrow stem cells or haemopoietic progenitors and characterized by clonal proliferation of one or more haemopoietic components in the bone marrow and, in many cases, the liver and spleen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the three major classifications of Myeloproloferative Disorders?

A
  1. Polycythaemia vera (PV).
  2. Essential thrombocythaemia (ET).
  3. Primary myelofibrosis (PMF).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the gene mutation associated with Polycythemia Vera?

A

JAK2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the Gene mutations associated with Essential thrombocythaemia?

A
  • JAK2
  • CALR
  • MPL - 5%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the gene mutations associated with Primary Myelofibrosis?

A
  • JAK2
  • CALR
  • MPL - 10%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the gene mutation associated with Mastocytosis?

A

KIT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the Gene mutation in Chronic Myeloid Leukaemia?

A

ABL1 ( fusion with BCR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of JAK2?

A

JAK2 has a major role in normal myeloid development by transducing signals from cytokines and growth factors including erythropoietin, granulocyte-colony stimulating factor receptor and thrombopoietin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where does the mutation of JAK2 (JAK2 V617F) occur?

A

The mutation occurs in a highly conserved region of the pseudokinase domain, which normally negatively regulates JAK2 signalling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the two types of JAK mutations that can occur?

A

JAK2- V617F ( 95%)
JAK 2 - Exon 12 ( the remainder)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the function of CALR?

A

CALR is a multifunction protein involved in signal transduction and gene transcription.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which epigenetic genes are associated in disease initiation?

A

TET2 and DNMT3A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which epigenetic genes are associated in disease progression?

A

ASXL1 and EZH2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

True or False? There is a five-fold increased incidence of myeloproliferative neoplasm in close relatives of patients, implying a genetic predisposition to the diseases.

A

TRUE!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Polycythaemia?

A

Polycythaemia is defined as an increase in the haemoglobin concentration above the upper limit of normal for the patient’s age and sex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the two major divisions of Polycythaemia?

A
  • Absolute polycythaemia or erythrocytosis - Red cell mass (volume) is raised to greater than 125% of that expected for body mass and gender.
  • Relative or Pseudopolycythaemia - the red cell volume is normal but the plasma volume is REDUCED .
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

True or False? If the haematocrit is higher than 0.60 there will always be a raised red cell mass and absolute polycythaemia.

A

TRUE!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

True or False? A haemoglobin (Hb) GREATER THAN 185 g/L or haematocrit GREATER THAN 0.52 in men, and
Hb GREATER THAN 165 g/L or Haematocrit GRETAER THAN 0.48 in women, indicates that erythrocytosis is likely.

A

TRUE !!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are factors that can increase erythropoietin?

A
  • Central hypoxia
  • Chronic lung disease
  • Right-to-left cardiopulmonary vascular shunts
  • Carbon monoxide poisoning
  • Obstructive sleep apnoea
  • High altitude
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Fill in the blanks. “ In Polycythemia Vera , the increase in red cell volume is caused by ________.”

A

A clonal malignancy of a marrow stem cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the major criteria for diagnosis of Polycythemia Vera according to WHO (2016)?

A
  1. High haematocrit (>49% in men, >48% in women) or high haemoglobin (>165g/L in men, >160g/L
    in women) or raised red cell mass (>25% above predicted)
  2. Bone marrow (BM) biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic mature megakaryocytes
  3. Presence of JAK2 V617F or JAK2 exon 12 mutation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is a minor criteria for the diagnosis of Polycythemia Vera according to WHO 2016?

A

Subnormal serum erythropoietin test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

True or False? Diagnosis of PV requires meeting either all three major criteria, or the first two major criteria and the minor criterion.

A

TRUE!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

In the three- stage approach for the diagnosis of Polycythemia Vera, what are the different components of Stage 1?

A

■ History and examination.
■ Arterial oxygen saturation (pulse oximetry)
■ Full blood count/film.
■ JAK2(V617F) mutation.
■ Serum erythropoietin level.
■ Serum ferritin.
■ Renal and liver function tests.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In the three- stage approach for the diagnosis of Polycythemia Vera, what are the different components of Stage 2?

A

■ Abdominal ultrasound.
■ Bone marrow aspirate and trephine.
■ Cytogenetic analysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

In the three- stage approach for the diagnosis of Polycythemia Vera, what are the different components of Stage 3>

A

■ Arterial oxygen dissociation (high oxygen-affinity haemoglobin).
■ Sleep study.
■ Lung function studies.
■ Gene mutations found in congenital polycythaemia
(e.g. EPOR, VHL, PHD2, HIF2A).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

True or False? Polycythemia Vera is normally a disease of all ages.

A

FALSE!! It is normally a disease of Old persons

Equal sex incidence!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the Clinical Features of Polycythaemia Veraa?

A

Clinical features result from hyperviscosity, hypervolaemia, hypermetabolism or thrombosis.

  • Headaches
  • Blurred vision
  • Night Sweats
  • Generalised pruritus especially after a hot bath
  • Plethoric appearance: ruddy cyanosis
  • Conjunctival suffusion and retinal venous engorgement.
  • Splenomegaly
  • Haemorrhage or thrombosis
  • Gout
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the Lab findings of Polycythaemia Vera?

A
  • INCREASED Haematocrit
  • INCREASED Haemoglobin
  • INCREASED red cell count & the total red cell volume.
  • Neutrophil leucocytosis
  • Increase in Basophils
  • Raised platelet count (50% patients)
  • A JAK2 mutation is present in the bone marrow and peripheral blood granulocytes in over 95% of patients.
  • The bone marrow is hypercellular with trilineage growth, as assessed by trephine biopsy.
  • Serum Eythropoetin is LOW!!
  • INCREASED Plasma Urate
  • Increased or normal LDH
  • Circulating erythroid progenitors (erythroid colony-forming unit, CFUE, and erythroid burst-forming unit, BFUE.
  • Chromosome abnormalities (e.g. deletions of 9p or 20q) are found in a minority of subjects. Mutations in genes TET2, ASXL1, DNMT3A, MPL, CBL, PPMID, SF3B1, NFE2, EZH2, SRSF2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Fill in the blanks. “ A gene mutation of _____ & _________ mutations predict for transformation to AML.”

A

TP53 and RUNX1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the treatment options for PV?

A
  1. Venesection
  2. Hydroxycarbamide ( hydroxyurea)
  3. JAK Inhibitors
  4. Interferon
  5. Aspirin
  6. Angiotensin-converting-enzyme (ACE) inhibitors
32
Q

Given an example of a JAK2 Inhibitor?

A

Ruxolitinib

  • fedratinib and pacritinib are in development.
33
Q

What are the congenital causes of Primary polycythaemia?

A
  • Mutations in genes that regulate oxygen sensing ( VHL ,PHD2 or HIF2A)
  • Mutation of Erythropoietin receptor gene ( EPOR)
  • Haemoglobin mutations that lead to high oxygen-affinity variants with subsequent tissue hypoxia.
34
Q

What is Essential Thrombocythaemia ?

A

In this condition there is a sustained increase in the platelet count due to megakaryocyte proliferation and overproduction of platelets.

35
Q

True or False? In Essential Thrombocythaemia,The haematocrit is normal and the Philadelphia chromosome or BCR-ABL1 rearrangement is absent.= and the bone marrow shows NO collagen Fibrosis

A

TRUE!!

36
Q

What is the Central diagnostic feature for Essential Thrombocythaemia?

A

A persisting platelet count of greater than 450 × 109/L.

37
Q

What are other causes of a raised platelet count that needs to be need to be fully excluded before an Essential Thrombocythaemia diagnosis can be made?

A
  • Iron Deficiency Anaemia
  • Inflammatory or malignant disorder
  • Myelodysplasia
38
Q

True or False? JAK 2 Exon 12 mutation is also associated with Essential Thrombocythaemia.

A

FALSE!! It is NOT see in ET.

39
Q

Mutation of which gene is seen in about 75% of JAK2-negative ET patients?

A

CALR

40
Q

What are the Clinical features of Essential Thrombocythaemia?

A
  • Thrombosis & Haemorrhage
  • JAK2 patients can present with Budd- Chiari syndrome- when the platelet count may be normal because of splenomegaly.
  • Erythromelalgia, a burning sensation felt in the hands or feet and promptly relieved by aspirin.
  • Splenomegaly
41
Q

What are the laboratory findings of Essential Thrombocythaemia ?

A
  1. Megakaryocytes
  2. Large platelets
42
Q

What are the Major criteria for diagnosis of Essential Thrombocythaemia according to WHO 2016?

A
  1. Sustained platelet count above 450×109/L
  2. Bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibre.
  3. No other myeloid malignancy, polycythaemia vera, primary myelofibrosis, chronic myeloid leukaemia (BCR-ABL1 positive) or myelodysplastic syndrome.
  4. Presence of an acquired pathogenetic mutation (in JAK2, CALR or MPL).
43
Q

What are the minor criteria for diagnosis of Essential Thrombocythaemia according to WHO 2016?

A
  1. Presence of a clonal marker.
  2. Absence of evidence for reactive thrombocytosis
44
Q

True or False? Diagnosis of essential thrombocythaemia requires meeting all four major criteria or the first three major criteria and one of the minor criteria.

A

FALSE!! Diagnosis of essential thrombocythaemia requires meeting all four major criteria or the first three major criteria and BOTH the minor criteria.

45
Q

What is the Treatment for ET?

A
  • Low-dose aspirin at 75 mg/day is generally recommended in all cases.
  • Patients with High risk - Platelet count over 1,500 be treated with Hydroxycarbamide or another cytoreductive agent to reduce the platelet count.
  • Low - risk patients are those aged below 60 years without a history of thrombosis or extreme thrombocytosis, and here ASPIRIN is sufficient.
46
Q

What are the side effects of Hydroxycarbamide?

A

Skin keratosis
Epitheliomas
Ulceration or pigmentation

47
Q

Which drug is the most widely used for treatment of ET?

A

Hydroxycarbamide

48
Q

Fill in the blanks. “ ______________ is is a good second-line treatment for ET but has cardiovascular side-effects, and a possible increased risk of myelofibrosis is also of concern.”

A

Anagrelide

49
Q

Patients diagnosed with ET who are pregnant , should be given which drug treatment?

A

α-Interferon

50
Q

What are the characteristics of the patients with Prefibrotic (early stage ) Primary Myelofibrosis?

A

Subjects tend to be:
- Younger
- Females
- Have smaller spleens
- Fewer cytopenias
- Fewer additional mutations (other than of JAK2, CALR or MPL)
- More thrombocytosis than those with overt PMF.

51
Q

What is the predominant feature of Primary Myelofibrosis?

A
  • Progressive generalized reactive fibrosis of the bone marrow in association with megakaryocyte atypia and proliferation.
  • Along with myeloid metaplasia or extra-medullary haemopoieisis ( with the development of haemopoiesis in the spleen and liver)
52
Q

True or False? Up to 50% of PMF present in a prefibrotic/early stage with no significant increase in reticulin or collagen, but markedly abnormal megakaryocytes in a hypercellular marrow.

A

TRUE!!

53
Q

What are the clinical features of Primary Myelofibrosis?

A
  • Massive Splenomegaly ( main physical findings)
  • Anaemia
  • Hypermetabolic symptoms such as loss of weight, anorexia, fever and night sweats are common.
  • Bleeding problems, bone pain or Gout occur in a minority of patients
54
Q

What are the Laboratory findings of Primary Myelofibrosis?

A
  • Normal or Increased Hb
  • The white cell and platelet counts are frequently high at the time of presentation. Later in the disease leucopenia and thrombocytopenia are common.
  • TEAR DROP poikilocytes
  • Trephine biopsy shows a fibrotic, hypercellular marrow. Silver staining shows a dense reticulin network except in Prefibrotic disease.
  • Increased Megakarycotyes
  • Increased bone formation (osteosclerosis)
  • Increased Serum Urate
  • Increased Serum LDH
  • JAK2 is mutated in approximately 60% of cases, CALR in ∼25% and MPL in ∼10%.
  • Transformation to AML occurs in 10-20%
55
Q

For Primary Myelofibrosis, which gene mutations can allow it to convert to AML?

A
  • The loss of the long arms of chromosomes 5 or 7,
  • An extra copy of chromosome 8 (trisomy 8)
  • Rearrangements of 11q23
56
Q

For Polycythaemia Vera which genetic mutations will predict for a transformation to AML?

A

TP53 and RUNX1

57
Q

Which drug used in the treatment of Primary Myelofibrosis can be used to reduce spleen size?

A

Ruxolitinib ( oral JAK2 inhibitor )

58
Q

During the treatment of Primary Myelofibrosis , which drug can be used to reduce splenomegaly and hypermetabolic symptoms?

A

Hydroxycarbamide

59
Q

Which drug can be used to prevent gout and urate nephropathy from hyperuricaemia in Primary Myelofibrosis?

A

Allopurinol

60
Q

Fill in the blanks. “For prefribrotic disease with no symptoms a ______________ approach should be taken.”

A

” Watch and Wait”

61
Q

True or False? In the prefibrotic disease, leukocytosis and thrombocytosis tend to be more marked and anaemia less than in overt disease.

A

TRUE!!

62
Q

What is Mastocytosis?

A

Mastocytosis is a clonal neoplastic proliferation of mast cells that accumulate in one or more organ systems.

63
Q

Which organs are normally involved in Systemic mastocytosis?

A

Bone marrow
Heart
Spleen
Lymph nodes
Skin

64
Q

What are the biomarkers for Mast cells?

A

CD2 and /or CD25 Positive

65
Q

What is the genetic mutation associated with Mastocytosis?

A

The somatic KIT mutation Asp816Val (D816V)

66
Q

Fill in the blanks. “ The most aggressive form of Mastocytosis is _________.”

A

Mast Cell Leukaemia

67
Q

What are the Clinical Features of Mastocytosis?

A
  • Flushing
  • Pruritus
  • Abdominal Pain
  • Bronchospasm
    *Urticaria pigmentosa
  • Serum TYRPTASE IS ELEVATED ( used for monitoring)
68
Q

What is the treatment for Mastocytosis?

A

Midostaurin is approved for treatment of systemic mastocytosis and avipritinib is also highly active.

69
Q

What is the MOA of Midostaurin and Avipritinib ?

A

They both inhibit the KIT tyrosine kinase

70
Q

In Chronic Neutrophilic Leukaemia the patients have a WBC count of?

A

OVER 25×109/L with at least 80% mature neutrophils

71
Q

What is the genetic mutation associated with Chronic Neutrophillic Leukaemia?

A

Activating mutations in the gene encoding the receptor for Colony-stimulating factor 3 (CSF3R)

72
Q

What are the clinical features of Chronic Neutrophillic Leukaemia?

A
  • High WBC ( over 25×109/L with at least 80% mature neutrophils)
  • No inflammation
  • no blast cells
  • no evidence for any other myeloproliferative neoplasm
  • MILD SPLENOMEGALY
73
Q

True or False? Chronic eosinophilic Leukaemia is a clonal persistent eosinophilia (greater than 1.5×109/L)

A

TRUE!!

74
Q

What is the genetic mutation associated with Chronic Eosinophillic Leukaemia ?

A

An interstitial lesion in chromosome 4 resulting in FIP1L1-PDGFRA fusion gene if present predicts for a response to tyrosine kinase inhibitors.

75
Q

True or False? In Chronic Eosinophillic Leukaemia, There may be greater than 5% but less than 20% blasts in the marrow.

A

TRUE!!

76
Q

What is the treatment for Chronic Eosinophillic Leukaemia for those not responding to Tyrosine Kinase Inhibitors?

A

Corticosteroids
Hydroxycarbamide
Interferon
Chlorodeoxyadenosine

77
Q

What are the genes associated with congenital polycythaemia?

A

VHL
PHD2
HIF2A

Clinical Haematology (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions