BCR TBL 10 - Pathology of Myeloid Cells

What is the most common mutation in essential thrombocythemia (ET)?

JAK2 V617F

Which MPN subtype has the highest risk of myelofibrotic transformation?

Polycythaemia vera

What is the role of CALR mutation testing?

To confirm clonal MPN in JAK2-negative ET or myelofibrosis

What are two complications of untreated PV?

Thrombosis and progression to myelofibrosis or AML

What is the main mechanism of thrombosis in MPNs?

Increased blood viscosity and dysfunctional platelets

What are common symptoms of myelofibrosis?

Weight loss, fatigue, massive splenomegaly, night sweats

What is the cause of teardrop cells in myelofibrosis?

Extramedullary hematopoiesis due to fibrotic marrow

What does a leukoerythroblastic blood film show?

Nucleated RBCs and immature granulocytes

What does a “dry tap” on bone marrow aspiration indicate?

Myelofibrosis or marrow infiltration

Which two mutations are most common in primary myelofibrosis?

JAK2 and CALR

What is the main driver of symptoms in myelofibrosis?

Cytokine release and extramedullary hematopoiesis

What therapy reduces splenomegaly in myelofibrosis?

JAK inhibitors like ruxolitinib

What is the clinical triad of PMF?

Anemia, splenomegaly, constitutional symptoms

What are the criteria for diagnosing essential thrombocythemia?

Persistent platelets >450, exclusion of reactive causes, clonal markers (JAK2, CALR, MPL)

What are common bleeding symptoms in ET despite high platelets?

Nosebleeds, bruising, GI bleeding (due to platelet dysfunction)

What is a microvascular complication of ET?

Erythromelalgia

What differentiates CMML from reactive monocytosis?

Persistent monocytosis >1 × 10⁹/L with dysplasia or clonal cytogenetics

What features overlap in MDS/MPN syndromes?

Cytopenias and proliferation (e.g., CMML)

What cytogenetic abnormality is associated with favorable prognosis in MDS?

Isolated del(5q)

Which MDS subtype carries the highest risk of AML progression?

MDS with excess blasts

What is the IPSS-R score used for?

Risk stratification in MDS

What is the blast threshold for AML diagnosis?

≥20% blasts in bone marrow or blood

What does MPO (myeloperoxidase) positivity indicate?

Myeloid lineage (AML)

What is the typical WBC count in APL?

Can be low, normal, or high—variable

Which AML subtype is a medical emergency?

APL (acute promyelocytic leukemia)

What is the first-line treatment in APL?

ATRA (all-trans retinoic acid)

What test confirms FLT3 mutation?

Molecular PCR testing

Which AML translocation is associated with gum infiltration and monocytic features?

t(9;11)

What defines therapy-related AML?

AML following prior chemo/radiation

What is a common therapy-related AML cytogenetic abnormality?

Complex karyotype or chromosome 5/7 deletion

Which population is most affected by MDS?

Elderly (median age ~70 years)

What does "ineffective hematopoiesis" mean in MDS?

Marrow produces cells that undergo apoptosis before maturing

What test shows ring sideroblasts?

Prussian blue stain of bone marrow aspirate

What are the lab features of MDS with ring sideroblasts?

Anemia + >15% ring sideroblasts

What is the most common presenting feature of MDS?

Anemia

What is the difference between primary and secondary AML?

Primary arises de novo; secondary follows MDS/MPN/chemo

What is the survival impact of FLT3 mutation in AML?

Poorer overall survival, higher relapse risk

What are the phases of ALL treatment?

Induction, consolidation, maintenance, CNS prophylaxis

Which ALL subtype is more likely to involve the mediastinum?

T-cell ALL

What immunophenotype confirms T-ALL?

CD3+, TdT+

What are the CNS prophylaxis methods in ALL?

Intrathecal chemotherapy (methotrexate), systemic high-dose therapy

What defines minimal residual disease (MRD)?

Molecular evidence of leukemia below morphological detection

Why is MRD testing important in leukemia?

Prognostic and guides therapy intensity

What is the hallmark of a leukemoid reaction?

Marked neutrophilia with left shift but high LAP score

How do you distinguish leukemoid reaction from CML?

Leukemoid = high LAP, no BCR-ABL; CML = low LAP, BCR-ABL+

What is the function of tyrosine kinase inhibitors in CML?

Block BCR-ABL–mediated proliferation

Which test monitors response to therapy in CML?

BCR-ABL PCR (quantitative)

What is complete molecular remission in CML?

Undetectable BCR-ABL by PCR

What does smudge cell represent pathologically?

Fragile lymphocyte disrupted during smear preparation

What defines Richter’s transformation?

CLL transforming into high-grade lymphoma (e.g., DLBCL)

What is the prognosis of Richter’s transformation?

Poor

What are common infections in CLL?

Encapsulated organisms (e.g., S. pneumoniae)

What is the role of BTK inhibitors?

Block B-cell signaling in CLL

What is a common side effect of ibrutinib?

Atrial fibrillation

What defines lymphocytosis?

4.0 × 10⁹/L lymphocytes in adults

What is the immunophenotype of hairy cell leukemia?

CD103+, CD11c+, TRAP+

What is a clinical feature of hairy cell leukemia?

Massive splenomegaly with pancytopenia

What is a classic BM finding in hairy cell leukemia?

“Fried egg” appearance of cells

What is the first-line therapy in hairy cell leukemia?

Cladribine (purine analogue)

Which leukemia has the best prognosis with treatment?

APL (if treated early)

Which leukemia subtype commonly presents with DIC?

APL (M3)

What is the role of arsenic trioxide in APL?

Used in combination with ATRA to induce remission

What indicates hematologic remission in leukemia?

Normal CBC + <5% blasts in marrow

What is the cause of bleeding in leukemia?

Thrombocytopenia and DIC (especially in APL)

What defines high-risk ALL?

Age >10, WBC >50,000, poor cytogenetics

What are supportive care measures in leukemia?

Transfusions, antibiotics, antifungals, tumor lysis prevention

What causes tumor lysis syndrome?

Rapid lysis of tumor cells → hyperuricemia, hyperkalemia, etc.

What is the treatment of tumor lysis syndrome?

Hydration, allopurinol, rasburicase

What test confirms CNS leukemia?

CSF cytology from lumbar puncture

What is the role of allogeneic stem cell transplant?

Potential curative therapy for high-risk/relapsed AML and ALL

When is allogeneic transplant indicated in AML?

Poor risk cytogenetics or refractory disease

What is graft-vs-leukemia effect?

Donor immune cells attack residual leukemic cells

What defines chronic phase in CML?

<10% blasts in blood/marrow

What defines accelerated phase in CML?

10–19% blasts or increasing counts/resistance

What defines blast crisis in CML?

≥20% blasts, resembles acute leukemia

Which cytogenetic abnormality is common in therapy-related AML?

Monosomy 7 or complex karyotype

What defines aplastic anemia (not leukemia but relevant differential)?

Hypocellular marrow with pancytopenia

How is aplastic anemia distinguished from MDS?

Aplastic: hypocellular, no dysplasia; MDS: hypercellular, dysplasia

What drug can cause aplastic anemia?

Chloramphenicol

What lab feature is common in ALL?

Pancytopenia with circulating lymphoblasts

What distinguishes lymphoblasts from myeloblasts on cytochemistry?

TdT+ for lymphoblasts; MPO+ for myeloblasts

What does high LDH suggest in leukemia?

High cell turnover

Which leukemia presents with mediastinal mass in adolescents?

T-cell ALL

What is the classic demographic for T-ALL?

Teenage males with mediastinal mass

What is the effect of JAK2 mutation on marrow?

Constitutive activation → proliferation of erythroid, megakaryocytic lines

What is a risk factor for secondary AML?

Prior alkylating agents (e.g., cyclophosphamide)

Which test distinguishes MDS from nutritional anemia?

Bone marrow biopsy with cytogenetics

What is the hallmark cytogenetic of APL?

PML-RARA fusion gene

What is the significance of t(8;21) in AML?

Favorable prognosis

What is the function of ATRA in APL?

Overcomes maturation arrest by PML-RARA

What is the diagnostic marker of megakaryocytes?

CD41 or CD61

What is the significance of elevated beta-2 microglobulin in CLL?

Poorer prognosis

What is the first sign of CLL progression?

Anemia or thrombocytopenia

What test is used to monitor disease burden post-chemotherapy in leukemia?

Minimal residual disease (MRD) testing

What is a common cause of low neutrophil count?

Viral infection, chemotherapy, autoimmune diseases, bone marrow failure

What is Felty’s Syndrome?

A triad of rheumatoid arthritis, neutropenia, and splenomegaly

Which leukemia is associated with the Philadelphia chromosome?

Chronic Myeloid Leukemia (CML)

What translocation defines the Philadelphia chromosome?

t(9;22)

Which gene fusion is involved in CML?

BCR-ABL

What is a key lab finding in CML?

Leukocytosis, basophilia, low LAP score, BCR-ABL+