Myeloid Malignancies Flashcards by Alice McQuade

2 Subgroups of Acute Leukaemia

Acute Myeloblastic

Acute Lymphoblastic

How well did you know this?

Not at all

Perfectly

Which myeloid malignancy is rapidly fatal but potentially curable?

Acute Myeloid Leukaemia

How well did you know this?

Not at all

Perfectly

Which cells fail to differentiate in Acute Myleoid Leukaemia?

Myeloid progenitor cells

How well did you know this?

Not at all

Perfectly

3 Clinical Features of AML

Bone Marrow Failure
Thromocytopenic bleeding
Infection

How well did you know this?

Not at all

Perfectly

Bone Marrow Failure experienced in AML causes which condition?

Anaemia

How well did you know this?

Not at all

Perfectly

Which types of infection are common in AML and why?

Bacterial and fungal

Neutropenia

How well did you know this?

Not at all

Perfectly

Why does bone marrow failure occur?

No differentiation of progenitor cells

Blast cells occupy >20% of bone marrow - visible on aspirate sample

How well did you know this?

Not at all

Perfectly

Features and sites of thrombocytopenic bleeding

Purpura and mucosal bleeding

Mucosal bleeding - rectal, urogenic, skin, heavy periods

How well did you know this?

Not at all

Perfectly

Example of a systemic fungal infection common in AML

Aspergillus fumigatus

How well did you know this?

Not at all

Perfectly

How do we investigate AML?

Blood count
Blood film
Bone marrow aspirate/trephine
Immunophenotyping of blasts
CSF Examination
Molecular genetics
NGS myeloid gene panel

How well did you know this?

Not at all

Perfectly

Which aquired gene mutations are associated with AML?

FLT3, NPM1, IDH1 &2

How well did you know this?

Not at all

Perfectly

Treatment of AML

Supportive for bone marrow failure
Chemotherapy
Allogeneic stem cell transplantation
All-Trans Retionoic Acid (ATRA) &amp; Arsenic Trioxide (ATO)
Targeted treatment

How well did you know this?

Not at all

Perfectly

Example of chemotherapy used in AML

Daunorubicin and cytosine arabinoside (DA)
Gemtuzumab
CPX 351

How well did you know this?

Not at all

Perfectly

Mechanism of gemtuzumab

Antibody with chemo attached

How well did you know this?

Not at all

Perfectly

Mechanism of CPX 351

Delivers DA in micelles

How well did you know this?

Not at all

Perfectly

In which specific condition is ATRA and ATO used?

Acute Promyelocytic Leukaemia

Bleeding out before treatment a big issue

How well did you know this?

Not at all

Perfectly

Example of targeted treatment in AML

Midostaurin where FLT3 mutation identified

How well did you know this?

Not at all

Perfectly

Features of Chronic Myeloid leukaemia

Anaemia
Splenomegaly
Weight loss
Hyperleukostasis
Gout

Lab results in CML

WBC high
Platelets High
Anaemia

Results on blood film in CML

Shows cells at all levels of differentiation

Basophil number high

Describe the state of bone marrow cellularity in CML

Hypercellular

Which genetic translocation occurs in the bone marrow and blood cells in CML

Philadelphia chromosomal translocation t(9;22)

Treatment of CML

Tyrosine Kinase Inhibitors TKI

Allogeneic Stem cell transplantation - only if TKI fail

Mechanism of TKI

Directly inhibit BCR-ABL

Examples of TKI

Imatinib (Glivec) Dasatinib Nilotinib

Name 3 Myeloproliferative Neoplasms

Polycythaemia Vera Essential Thrombocythaemia (ET) Idiopathic Myelofibrosis

Features of blood results in Polycythaemia Vera

High red cells High white cells High platelets

Polycythaemia Vera can occur secondary to...

Chronic Hypoxia

Which mutation is common to all 3 MPNs?

JAK2 V617F 95% PV 50% ET &Myelofibrosis

Which 2 mutations can occur in ET?

JAK2 V617F | CALR

JAK2 is autophosphorylated upon the binding of which molecule?

EPO

Autophosphorylation of JAK2 leads to downstream signalling to promote which process?

Red cell production

What happens when JAK2 is mutated in MPN?

JAK2 is autophosphorylated even in absence of EPO | Leads to Myeloproliferative red cell production

Clinical features of Polycythaemia vera

``` Headache Itch - aquagenic pruritus Vascular occlusion Thrombosis TIA Stroke Splenomegaly ```

Lab results in Polycythaemia Vera

High haematocrit Raised white cell and platelet count Raised uric acid Measure blood volume to see true increase in red cell mass

Treatment of Polycythaemia vera

Venesection Aspirin Hydroxycarbamide Ruxolitinib (JAK2 Inhibitor) - only if hydroxycarbamide fails and exhibiting systemic symptoms

High haematocrit causes what clinical symptom/sign

Sluggish circulation

Poor management/control of PV can lead to..

Thrombosis and stroke Bone marrow failure Transformation to AML

PV can be a precursor to which condition if not treated successfully?

AML

Sign of essential thrombocytopenia

Raised platelet count

Which genetic mutations are present in ET

JAK2 in 50% | CALR 25%

Symptoms of ET

Arterial and venous thrombosis | Digital ischaemia- erythromyalgia, vascular occlusion

Treatment of ET

Aspirin Hydroxycarbamide Anagrelide

Signs of ET on blood film

Marked thrombocytosis with giant platelets