PATHO - WBC and Lymph Nodes 4 (Myeloid)

Hematopoietic stem cell

Which cell type is pluripotent and capable of self-renewal?

Multipotent progenitor

Which progenitor is more proliferative with less self-renewal?

Committed precursors

Which precursors have limited potential and cannot self-renew?

Erythropoietin

Name the growth factor primarily driving erythroid lineage.

Thrombopoietin

Name the growth factor primarily driving megakaryocyte/platelet lineage.

G-CSF

Name a growth factor that stimulates granulocytic lineage.

GM-CSF

Name the growth factor that stimulates granulocytic and monocytic lineages.

Feedback loop

What regulatory system tightly controls hematopoiesis?

More lineages

If a transformed cell is higher in progenitor hierarchy, how many lineages are affected?

Growth factors

What influences committed precursors toward a specific lineage?

Clonal hematopoiesis

What term describes a clone with an acquired pathogenic mutation but normal blood counts?

TET2

Name one of the most commonly mutated genes in clonal hematopoiesis.

DNMT3A

Name another commonly mutated gene in clonal hematopoiesis.

DNA methylation

What molecular process do TET2 and DNMT3A regulate?

1% (per year)

What percent per year risk converts clonal hematopoiesis to a hematopoietic neoplasm?

Cardiovascular disease

Clonal hematopoiesis increases risk for which noncancer mortality cause?

TET2

Which mutation reprograms monocytes/macrophages and increases inflammation?

RDW

What laboratory parameter can be increased and predict mortality in clonal hematopoiesis?

Asymptomatic

Typical symptom status of clonal hematopoiesis with normal counts?

Myeloid neoplasms

Clonal hematopoiesis most frequently transforms into which neoplasm group?

Increases with age

Age effect on clonal hematopoiesis risk?

Cytosine deamination

Mutation mechanism often causing clonal hematopoiesis (base change)?

>=20%

Minimal marrow blast percentage for AML diagnosis?

PML-RARa

AML with t(15;17) forms which fusion gene?

RUNX1-RUNX1T1

AML with t(8;21) forms which fusion gene?

CBFB-MYH11

AML with inv(16) forms which fusion gene?

Transcription factor mutations

What class of mutations block myeloid differentiation by altering transcription factors?

Signaling protein mutations

Which mutation class results in constitutive growth/survival signaling in AML?

FLT3

Name a common signaling protein mutated in AML.

Epigenome regulators

Mutations in which category produce abnormal DNA methylation in AML?

Complex karyotype

TP53 mutations in AML associate with what karyotype pattern?

5 and 7

Therapy-related AML commonly shows deletions of which chromosomes?

APL

AML with t(15;17) is also called what leukemia subtype?

Myeloblasts

Auer rods are needle-like granules characteristic of which cell?

Monoblasts

Which blast type shows folded or lobulated nuclei and is nonspecific esterase positive?

t(15;17)

Which AML subtype has the best prognosis overall?

t(8;21) and inv(16)

Which two AML cytogenetic abnormalities have good prognosis with chemo?

DIC

Name a clinical consequence from procoagulant release in AML, especially APL.

Pancytopenia

Primary clinical presentation of AML (cellular level)?

100,000/µL

Typical peripheral blast count range in AML patients varies and may be above what?

Immunophenotypimg

Which diagnostic method differentiates myeloblasts from lymphoblasts?

AML (exception)

If blasts are <20% but a specific genetic aberration is present, diagnosis is?

Delicate chromatin

Describe nuclear chromatin of myeloblasts.

2-4

Typical number of nucleoli seen in myeloblasts.

Auer rods

What cytoplasmic structure is characteristically seen in some myeloblasts?

Mouth and skin

Most common infection sites in AML patients due to neutropenia?

Mucosal bleeding

Common bleeding presentation in AML from thrombocytopenia?

Fatigue

Major symptom from anemia in AML.

Bone marrow exam

What test is essential to exclude acute leukemia in pancytopenia?

Fever

AML patients often have what fever-related sign due to infection?

Infective hematopoiesis

MDS refers to clonal stem cell disorders with what major defect?

Dysplasia

MDS is characterized by abnormal cell shape known as what?

Epigenetic factors

Name one class of proteins commonly mutated in MDS affecting epigenetics.

RNA splicing factors

Name the mutated machinery class in MDS that affects transcript processing.

RUNX1

Loss-of-function mutations in which transcription factor occur in MDS?

~10%

What percentage of MDS cases have p53 loss-of-function?

Monosomy 5

Recurrent chromosomal abnormality commonly seen in both primary and t-MDS.

Monosomy 7

Another common chromosomal abnormality in MDS.

Trisomy 8

Which chromosomal trisomy is associated with MDS?

Rapidly

Therapy-related MDS often transforms to AML how quickly?

Hypercellular

Bone marrow cellularity at MDS diagnosis is usually?

Ring sideroblasts

What marrow erythroid abnormality with iron-laden mitochondria is seen in MDS?

Pseudo-Pelger-Huet

Name neutrophils with only two nuclear lobes seen in MDS.

Pawn-ball megakaryocytes

What megakaryocyte abnormality with multiple separate nuclei is seen in MDS?

10%

Peripheral blood blast percentage in MDS is typically less than what?

Giant platelets

What platelet finding is common in peripheral smear of MDS?

Macrocytes

What red cell size abnormality is commonly seen in MDS?

Abnormal shapes

What peripheral smear finding indicates poikilocytosis?

Monocytosis

What circulating cell increase may accompany some MDS cases?

<20%

Marrow myeloid blasts in MDS are increased but remain below what percent?

70 years 

Typical mean age for MDS presentation.

Pancytopenia

Major clinical syndrome caused by MDS cytopenias.

4-8 months

Median survival for therapy-related MDS (t-MDS).

AML

MDS progression risk: all forms can transform to what?

Tyrosine kinase

Common pathogenic feature of MPNs involves constitutively activated what?

Organomegaly

MPNs often cause extramedullary hematopoiesis leading to what sign?

Fibrosis

MPNs can progress to a spent phase dominated by what marrow change?

AML

MPNs can variably transform into what acute malignancy?

JAK-STAT

Which signaling pathway is commonly activated in MPNs?

Hematopoietic stem cell

MPN neoplastic stem cells commonly originate from what?

t(9;22)

Chromosomal translocation defining CML?

BCR-ABL

Name the fusion gene created in CML.

22

The Philadelphia chromosome is which chromosome derivative?

Tyrosine kinase

BCR-ABL causes constitutive activation of which type of enzyme?

100,000/uL

Typical peripheral white blood cell count in CML can exceed what?

Different stages

What cell maturation pattern is seen in CML peripheral blood?

<10%

Percentage of blasts in CML chronic phase is usually less than what?

Spleen

Which organ is markedly enlarged in CML due to extramedullary hematopoiesis?

3 years

Early natural history untreated median survival for CML?

Thrombocytopenia

CML accelerated phase often features increasing basophilia and what cytopenia?

Dimerization

The BCR moiety contains a domain that promotes what to activate ABL?

Sea-blue histiocytes

Name marrow macrophages with wrinkled blue cytoplasm seen in CML.

Panmyelosis

PV is characterized by increased production of which three lineages?

JAK2

The key mutation in PV occurs in which gene?

V617F

Specific JAK2 amino acid substitution in PV.

Erythropoietin

PV patients have decreased requirement for which hormone?

Plethora

Name the classic clinical sign from increased red cell mass in PV (skin).

Pruritus

Common symptom of PV triggered by basophil/histamine release causing skin itching.

Hyperuricemia

PV increases risk for what metabolic complication from high cell turnover?

Increased

Typical platelet count trend in PV.