chronic myeloid leukemia (CML) chromosomal abnormality - Answers Philadelphia chromosome
(~95% of cases)
polycythemia vera (PV) chromosomal abnormality - Answers JAK2V617F mutation (most cases)
chronic myeloproliferative disorders - Answers -chronic myeloid leukemia (CML)
-polycythemia vera (PV)
-essential thrombocythemia (ET)
-primary myelofibrosis (PMF)
-chronic neutrophilic leukemia (CNL)
-chronic myelomonocytic leukemia (CMML)
-juvenile myelomonocytic leukemia (JMML)
polycythemia vera major criteria (WHO) - Answers -hemoglobin >16.5 g/dL (men), >16 g/dL (women)
-Hct >49% (men), >48% (women)
-increased RCM >35 mL/kg (men), >31 mL/kg (women)
-BM biopsy with hypercellularity and panmyelosis
-presence of JAK2V617F or JAK2 Exon 12 mutations
polycythemia vera minor criteria (WHO) - Answers subnormal serum EPO levels
chronic myeloid leukemia (CML) - Answers -etiology: a single genetic translocation in a pluripotent
hematopoietic stem cell causes clonal overproduction of immature neutrophils, usually diagnosed
between age 45-55
-chromosomal abnormality: Philadelphia chromosome
-morphology: myeloblasts, promyelovytes, bands, segmented neutrophils (all stages of neutrophil
development) seen in the peripheral blood, nRBCs present, *gaucher-like macrophages present*, very
small megakaryocytes present
-symptoms: infections with Strep pneumoniae, anemia, bleeding, splenomegaly
-PB: RBCs normal to inc, retics normal, total WBCs increased, granulocytes increased (neutrophils,
basophils, eosinophils), PLTs normal to inc, *LAP stain decreased*
-BM: hypercellular, increased granulopoiesis, decreased erythropoiesis, megakaryopoiesis increased,
reticulin fibers increased
chronic myeloid leukemia (CML) stages - Answers chronic phase (3-4 years) → accelerated phase →
blastic phase → possible transition to acute leukemia (poor prognosis)
chronic myeloid leukemia (CML) treatments - Answers -BM transplant or SCT= CURE
-*gleevec* (imatnib mesylate)
-sprycel, dasigna, bosulib, iclusig
polycythemia vera (PV) - Answers -etiology: neoplastic clonal stem cells mature independently of EPO
stimulation, causing panmyelosis with a predominate increase in erythrocytes (grans and PLTs can be
increased too)
-Chromosomal abnormality: JAK2V617F mutation
-morphology: N/N RBCs, teardrop cells (dacrocytes) present
-symptoms: triad of BM fibrosis, splenomegaly and anemia w/ teardrop cells (dacrocytes)
-lab findings: Hgb/ Hct/ RCM increased, low serum EPO levels
-PB: RBCs increased, total WBCs increased, granulocytes increased, PLTs increased, *LAP stain normal
to inc.*
-BM: hypercellular, normoblasts (immature RBCs) increased, granulocytes increased, megakaryocytes
increased, reticulin fibers increased
polycythemia vera (PV) treatments - Answers -therapeutic phlebotomy: bring Hct ≤45%
-hydroxyurea
-busulfan
-JAK inhibitors: Ruxolitinib, Lestaurtinib
essential thrombocythemia (ET) - Answers -etiology: clonal myeloproliferative neoplasm leading to
increased megakaryopoiesis and thrombocytosis
-chromosomal abnormality: JAK2V617F most common, CALR and MPL mutations also common
(others possible: MPL W515L/K, TET2, ASX1, LNK, IDH1/2)
-morphology: giant, agranular platelets, platelet clusters, RBCs are N/N
-symptoms: vascular occlusion in digits, veins & arteries, splenomegaly, erythromyelalgia (throbbing/
burning in hands and feet)
, -PB: *increased PLT count* (≥450*10⁹/L) , Hgb/Hct slightly decreased, RBC count normal, total WBCs
normal to inc, segmented neutrophils increased, *platelet function decreased*
-BM: hypercellular, increased megakaryocytes, large/ variably sized megs with hyperlobulated/ dense
nuclei, clusters of megs, mainly proliferation of megakaryocytes is seen, erythropoiesis increased,
*reticulin fibers normal to mildly inc.*
essential thrombocythemia (ET) treatments - Answers -hydroxyurea
-JAK2 inhibitors: Ruxolitinib, Lestaurtinib
-low dose aspirin (prevents thromboses)
primary myelofibrosis (PMF) - Answers -etiology: splenomegaly and ineffective hematopoiesis caused
by hypercellularity, fibrosis and increased megakaryocytosis of the bone marrow
-chromosomal abnormality: JAK2V617F most common (also possible: MPL W515L/K, CBL, TET2,
ASXL1, LNK, EZH2, IDH1/2)
-morphology: tear drop cells (dacrocytes), nRBCs, anisocytosis, poikilocytosis, polychromasia,
abnormal platelets and micromegakaryocytes present
-symptoms: fatigue, pruritis (itching), bone pain, palpitations, night sweats, splenomegaly,
hepatomegaly
-Lab findings: Hgb normal to decreased
-PB: normoblasts (immature RBCs) increased, immature granulocytes increased, total WBCs variable,
PLT count variable, megakaryocytes present, LAP stain variable
-BM: *INTENSE fibrosis* (lots of reticulin and collagen fibers), hypercellular, increased granulocytes
and megakaryocytes, erythropoiesis and myelofibrosis increased, sinuses increased,
dysmegakaryopoiesis and dysgranulopoiesis present
-*dry tap on bone marrow aspiration due to extent of fibrosis*
primary myelofibrosis (PMF) treatments - Answers -hydroxyurea
-JAK2 inhibitors: Ruxolitinib, Lestaurtinib
-CYT387
-TG101348
chronic neutrophilic leukemia (CNL) - Answers -etiology: rare clonal disorder that causes
hyperproliferation of neutrophilic cells in the bone marrow, may progress to AML
-chromosomal abnormality: +8, +9, +21, Del(20q), Del(11q), del(12p), philadelphia chromosome *NOT
* implicated
-morphology: *extreme neutrophilia*, increased neutrophil precursors (segmented neutrophils,
bands), neutrophils containing toxic granules, decreased monocytes, RBCs and PLTs are normal
-symptoms: hepatosplenomegaly, mucocutaneous bleeds, gout, pruritis (itching)
-PB: extreme neutrophilia (<70% of cells), WBC count increased >25x10⁹/L, monocytes decreased <
1x10⁹/L
-BM: hypercellular, increased neutrophils, myeloblasts >5% of nucleated cells
chronic myelomonocytic leukemia (CMML) - Answers -etiology: malignant hematopoietic stem cells
lead to bone marrow dysplasia and monocytosis, may transition to AML
-chromosomal abnormality: deletion of chromosome 7, trisomy 8
-morphology: monocytes make up ≥10% total WBCs in PB
-symptoms: hepatoplenomegaly
-PB: ≥20% blasts, persistent monocytosis >1*10⁹/L, increased monocytes
-BM: ≥20% blasts, BM dysplasia
juvenile myelomonocytic leukemia (JMML) - Answers -etiology: aggressive hematopoietic disorder
that presents in childhood (~2 years old)
-chromosomal abnormality: 1. PTPN-11, K-RAS, N-RAS, CBL or NF1 mutations seen in ~90% of cases,
Philadelphia chromosome *NOT* implicated
-morphology: dysplsatic/ abnormal monocytes
-symptoms: splenomegaly, anemia
-PB: leukocytosis, monocytosis (≥ 1*10⁹/L), thrombocytopenia, >20% blasts
-BM: increase of myeloid and monocytic cells (hypercellular), >20% blasts
chronic myeloid leukemia (CML) accelerated phase criteria (WHO) - Answers -poor response to
therapy
-anemia is increased (hemoglobin is decreased)
-mature WBCs decreased
-basophils increased