Study guide
7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms
Key Takeaways Explain This Topic AI
Acute leukemia, chronic leukemia and marrow infiltration disorders appear under both leukocyte disorders and hematologic malignancies.
Acute promyelocytic leukemia is a medical emergency in which all-trans retinoic acid is started on clinical suspicion before cytogenetic confirmation.
Chronic myeloid leukemia is defined by the BCR-ABL1 fusion and treated with a tyrosine kinase inhibitor.
Asymptomatic early-stage chronic lymphocytic leukemia is observed rather than treated, since early therapy does not improve survival.
Differentiation syndrome during all-trans retinoic acid therapy presents with fever, dyspnea, infiltrates and weight gain and is treated with dexamethasone.
Last updated: August 2026
Hematologic neoplasms arise from the malignant transformation of myeloid, lymphoid, or plasma cell lineages at various stages of differentiation. Board certification requires precise understanding of molecular cytogenetics, risk stratification, targeted antineoplastic pharmacology, and oncologic complications.
1. Acute Leukemias
Acute leukemias are characterized by the rapid clonal proliferation of poorly differentiated, immature hematopoietic progenitor cells (blasts) in the bone marrow, resulting in bone marrow failure (anemia, neutropenia, thrombocytopenia) and tissue infiltration.
Acute Leukemia Subtype Hallmark Morphology & Flow Cytometry Characteristic Cytogenetics / Molecular Clinical Features & Board Pearls Evidence-Based Therapy
Acute Myeloid Leukemia (AML) ≥ 20% myeloblasts in marrow or blood; delicate Auer rods (fused azurophilic granules, peroxidase+); CD13+, CD33+, CD34+, CD117+, MPO+ Favorable: t ( 8 ; 21 ) t(8;21) t ( 8 ; 21 ) , i n v ( 16 ) inv(16) in v ( 16 ) , NPM1 or biallelic CEBPA without FLT3-ITD .; Adverse: FLT3-ITD , TP53 , complex karyotype, del(5q), del(7) Pancytopenia, gingival hyperplasia (monocytic AML-M5), leukemia cutis, myeloid sarcoma Induction: "7+3" Regimen (Cytarabine 7-day continuous infusion + Daunorubicin x 3 days). Add Midostaurin for FLT3 mutations. Consolidation: High-dose Cytarabine (HiDAC) or Allogeneic HCT for intermediate/poor risk
Acute Promyelocytic Leukemia (APL / AML M3) Hypergranular promyelocytes with bundles of multiple Auer rods ( "faggot cells" ); CD33+, CD13+, CD34-negative, HLA-DR-negative Translocation t ( 15 ; 17 ) ( q 24 ; q 21 ) t(15;17)(q24;q21) t ( 15 ; 17 ) ( q 24 ; q 21 ) creating the PML-RARA fusion transcript MEDICAL EMERGENCY: Consumptive coagulopathy / severe DIC (hyperfibrinolysis, fatal intracranial/pulmonary hemorrhage) EMERGENCY THERAPY: Immediate All-trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) upon suspicion. Monitor for Differentiation Syndrome (treat with IV Dexamethasone 10 mg BID)
Acute Lymphoblastic Leukemia (ALL) Lymphoblasts with high nuclear-to-cytoplasmic ratio; TdT+ ; B-ALL: CD19+, CD20+, CD22+; T-ALL: CD3+, CD5+, CD7+ t ( 9 ; 22 ) ( q 34 ; q 11.2 ) t(9;22)(q34;q11.2) t ( 9 ; 22 ) ( q 34 ; q 11.2 ) BCR-ABL1 (Philadelphia chromosome) in 25–30% of adults; t ( 4 ; 11 ) t(4;11) t ( 4 ; 11 ) KMT2A rearrangement B-ALL: Bone pain, hepatosplenomegaly, testicular enlargement.; T-ALL: Adolescent male with anterior mediastinal mass (stridor, SVC syndrome) Multi-agent induction (Vincristine, Corticosteroids, Anthracycline, PEG-asparaginase). If Ph+ ALL: Add BCR-ABL TKI (Dasatinib/Ponatinib). Intrathecal Chemotherapy (Methotrexate) is mandatory for CNS prophylaxis
- 2. Chronic Leukemias & Myeloproliferative Neoplasms (MPNs)
- Chronic Myeloid Leukemia (CML)
Pathophysiology: Clonal myeloproliferative disorder driven by the balanced translocation t ( 9 ; 22 ) ( q 34 ; q 11.2 ) t(9;22)(q34;q11.2) t ( 9 ; 22 ) ( q 34 ; q 11.2 ) , which fuses the BCR gene on chromosome 22 with the ABL1 tyrosine kinase gene on chromosome 9 ( Philadelphia Chromosome ). This creates the constitutively active BCR-ABL1 oncoprotein kinase , driving uncontrolled granulopoiesis.
Clinical Presentation: Marked leukocytosis (WBC often 50,000–250,000/mcL) with the complete spectrum of myeloid differentiation (myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands, neutrophils), absolute basophilia and eosinophilia , and massive splenomegaly . Leukocyte Alkaline Phosphatase (LAP) score is low/zero (differentiates CML from a reactive leukemoid reaction where LAP is elevated).
Disease Phases:
Chronic Phase: < 10% blasts in marrow/blood (85–90% of presentations).
Accelerated Phase: 10–19% blasts, persistent thrombocytopenia (< 100k) or thrombocytosis (> 1,000k), progressive splenomegaly.
Blast Crisis: ≥ 20% blasts in marrow/blood or extramedullary blast proliferation (acts as acute leukemia: 70% myeloid, 30% lymphoid).
Targeted Management:
First-line: Tyrosine Kinase Inhibitors ( TKIs: Imatinib [1st gen], Dasatinib, Nilotinib, Bosutinib [2nd gen]).
Monitoring: Quantitative Real-Time PCR (RT-qPCR) for BCR-ABL1 transcripts on the International Scale (IS) every 3 months. Milestone: Major Molecular Response (MMR / M R 3.0 MR^{3.0} M R 3.0 : BCR-ABL1 ≤ 0.1 % \le 0.1\% ≤ 0.1% IS) at 12 months.
Resistance / Mutations: The T315I gatekeeper mutation confers resistance to all 1st and 2nd generation TKIs; requires Ponatinib (3rd gen TKI) or Asciminib (allosteric STAMP inhibitor).
Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
Diagnostic Criteria: Sustained absolute monoclonal B-lymphocytosis ( ≥ 5 , 000 / mcL \ge 5,000/\text{mcL} ≥ 5 , 000/ mcL ) in peripheral blood for ≥ 3 \ge 3 ≥ 3 months. Flow cytometry reveals co-expression of CD5, CD19, CD20 (dim), CD23 , and weak surface immunoglobulin light chain restriction (kappa or lambda). Smear shows mature small lymphocytes with fragile smudge cells (basket cells) .
Staging Systems:
Rai System: Stage 0 (Lymphocytosis alone, low risk); Stage I (Lymphadenopathy); Stage II (Splenomegaly or hepatomegaly); Stage III (Anemia, Hb < 11.0 g/dL); Stage IV (Thrombocytopenia, Platelets < 100,000/mcL).
Binet System: Stage A (< 3 lymph node areas); Stage B ( ≥ 3 \ge 3 ≥ 3 lymph node areas); Stage C (Anemia Hb < 10 or Platelets < 100k).
Indications for Treatment (iwCLL Criteria):
Asymptomatic early-stage disease (Rai 0–II without active disease) is managed with active surveillance ("watch and wait") ; early treatment does NOT prolong overall survival.
Initiate treatment ONLY for active disease: Progressive marrow failure (worsening anemia/thrombocytopenia), massive/progressive splenomegaly ( ≥ 6 \ge 6 ≥ 6 cm below costal margin), bulky/progressive lymphadenopathy ( ≥ 10 \ge 10 ≥ 10 cm), progressive lymphocytosis with lymphocyte doubling time < 6 months, or severe disease-related B symptoms.
Modern First-Line Targeted Therapies:
BTK Inhibitors: Acalabrutinib or Zanubrutinib (preferred over ibrutinib due to lower rates of atrial fibrillation and bleeding) continuous daily therapy.
BCL-2 Inhibitor Regimen: Fixed-duration Venetoclax + Obinutuzumab (anti-CD20) x 12 months (requires tumor lysis syndrome prophylaxis and stepped dose titration).
High-risk genetics: Deletion 17p / TP53 mutation renders chemoimmunotherapy (FCR) ineffective; targeted therapy with BTK inhibitors or Venetoclax is mandatory.
Classical Myeloproliferative Neoplasms (MPNs)
MPN Entity Driver Mutations Key Laboratory & Bone Marrow Findings Classic Clinical Features Evidence-Based Therapy
Polycythemia Vera (PV) JAK2 V617F (> 95%) or JAK2 Exon 12 (3%) Elevated Hct (> 49% men, > 48% women), Low serum Erythropoietin (EPO) , panmyelosis on marrow Aquagenic pruritus (severe itching after warm bath), erythromelalgia, splenoportal venous thrombosis, hyperuricemia/gout Therapeutic Phlebotomy (Target Hct < 45% strictly) + Aspirin 81 mg daily .; Add Hydroxyurea for High Risk (Age ≥ 60 \ge 60 ≥ 60 or prior thrombosis)
Essential Thrombocythemia (ET) JAK2 V617F (55%), CALR (25%), MPL (4%) Sustained Platelets ≥ 450 , 000 / mcL \ge 450,000/\text{mcL} ≥ 450 , 000/ mcL , large mature megakaryocytes in marrow Microvascular vasomotor symptoms (headache, erythromelalgia), thrombosis, paradoxical bleeding (acquired vWS if Plt > 1 million) Low-dose Aspirin.; Add Hydroxyurea (or Anagrelide) for High-Risk patients (Age ≥ 60 \ge 60 ≥ 60 or prior thrombosis)
Primary Myelofibrosis (PMF) JAK2 (60%), CALR (25%), MPL (5%) Leukoerythroblastic blood smear , Teardrop erythrocytes (Dacrocytes) , dry tap marrow ( reticulin/collagen fibrosis ) Massive splenomegaly (extramedullary hematopoiesis), severe cachexia, constitutional B symptoms, bone pain Ruxolitinib or Fedratinib (JAK1/2 inhibitors) to shrink spleen and relieve symptoms; Allogeneic HCT is the sole curative option