Hematopoiesis

Leukemia: Myeloid or Lymphoid

MPS

AML

RBCs

Erythroblasts

Neutrophils

Myeloblasts

Eosinophils

Myeloid Stem Cell

Basophils

Hematopoietic
Stem Cell (CD34+)

Monoblasts

Monocytes

Megakaryoblast

Megakayrocytes

B Lymphoblasts

ALL/L

Naive B cells

Lymphoid Stem
Cell

Plasma Cells
CD8+ T cells

T Lymphoblasts

Naive T cells
CD4+ T cells

Sign and Symptoms of Lymphoid Leukemia

Mostly from malignant cells taking up BM space
-Anemia and fatigue
-Neutropenia and infections/fever
-Thrombocytopenia with petechiae/bruising
-Bone pain from expansion of BM
-CNS symptoms

Signs and Symptoms of Lymphoid Lymphomas

-Lymphadenopathy; may wax and wane from month
to years, grow over weeks or days.
-enlarged lymph nodes are usually painless and show
no signs of inflammation such as erythema or
discharge
-extranodal sites seen in ~1/3 of pts; BM, GI and skin
are most common signs
-B Symptoms (1) unexplained fever over 38C,
(2)drenching night sweats, (3)unexplained weight
loss greater than 10% if total body weight

Myeloid Neoplasms
Acute Myeloid Leukemia
(AML)

Acute

-inc blast >20%

Acute Promyelocytic Leukema

-Cytopenia

-Hypergranular promyelocytes w/ lots of auer

rods in each

-older ppl
-MPNs/MDS -> AML

-DIC!

-pancytopenia

-t(15; 17) -> fusion protein whih blocks

differentiations

-infiltrate in gingiva

-tx: All trans retinoic acid (ATRA)

-auer rods in cyto of

myeloblasts!

Chronic Myelogenous Leukemia (CML)

-Neutrophilia with left shift, with absolute
basophilia and eosinophilia
Myeloid Neoplasms

-bcr-abl +ve\
-Tx:Gleevec - blocks ATP binding to CML
enzyme

Polycythemia Vera
-proliferation of erythrocytes
Myeloproliferative Neoplasm

-Head Sx (headache, dizziness, visual

disturbance, parasthesias)

(MPN)

-JAK is always on w/out it's ligand EPO

- inc mature cells

-splenomegaly
-mutation in Tyr kinase -> MAPK
constitutively active

Essential Thrombocytosis
-sustained thrombocytosis
-TIAs. gangreen, Budd-Chiari
-platelets are high but normal

Chronic
Myelodysplastic Syndrome
(MDS) - dec; disordered
maturation
-older ppl - 70yrs

Primary Myelofibrosis (PMF)

inc cellularity but ineffective

hematopoiesis so cytopenia

-splenomegaly, thrombosis, leukocytosis

-Presents w/ normocytic or
macrocytic anemia

-extramedullary hematopoiesis in spleen

-ringed sideroblasts

-JAK-2 mutation but no bcr-abl mutation

-extensive fibrosis in BM -> dry tap

Lymphoid Neoplasms

B-ALL
- Chd (85% in chd)
-"leukemic" presentation, B Sx
-Px favorable for chd (85% remission)

Acute/Precursor
s

Acute Lymphoblastic
Leukemia
T-ALL
-late childhood, adolescence or YA;
- "lymphomic" presentation
-typically teen male with adenopathy or
bulky mediastinal mass => SVC syndrome or
tracheal obstruction
-Generally worse Px

Lymphoid
Neoplasms

Non-Hodgkin's Lymphoma - See Below...

Hodgkins
Mature B Cell

- Aggressive, X'tic and predictable pattern, curable!

-from single or chain of LN -> spreads to
neighboring nodes -> spleen and BM
-Young women, 32 yrs
-Histo: Scattered Reed-Steinberg cells (owl eyes) on
a background of inflammatory cells

Mature

Mycosis Fungoides
-Most common T cell lymphoma,
cutaneous, flat -> plaque -> tumor
Mature T Cells

-small cells with convoluted nuclei,

invading skin and blood
-may -> Sezary Syndrome (blood and
lymph node involvement and a rash
covering entire body)

...Mature B cell contd

Chronic Lymphoctytic Leukemia (CLL)/Small
Lymphocytic Leukemia (SLL)
-Most common leukemia in adults!
-sustained lymphocytosis >5000/L
-Immunodeficiency (as CLL lymphos are non-fxnal,
auto-Ab against normal cells) -> infections, anemia
, thrombocytopenia -> DLBCL
-Good Px: Del 13q, 11q, trisomy 12
-Poor Px: del 17q (p53 gene)
Hairy Cell Leukemia
-cytopenias, monoctyopenias w/ neutropenia
-splenomegaly, "B" symptoms
Indolent (months to
years/ incurable or
chronic)

-Hairy cells w/ abundant cyto, inc red pulp in

spleen
-Mutation in BRAF gene, Tx:BRAF inhibitor

Follicular Lymphoma
-middle aged, indolent
-t (14; 18), bcl-2+ Ig H (upreg anti-apoptotic signal)
-follicular-looking nodules in nodes but no distinct parts
of the node present
Extra nodal marginal zone lymphoma of mucosal assoc
lymphoid tissue (MALToma)
-occurs in pts w/ chronic inflammation. ex. autoimmune, from
polyclonal -> monoclonal B cell lymphoma
-Highly assoc with H. pylori (lymphoepithelial lesions)
Non-Hodgkin's B
Lymphoma/
Mature B Cells

Diffuse Large B cell (DLBCL)

-mean age 60yrs
-40% of all NHL
-aggressive symptomatic mass
-5yr Survival 60%
Aggressive (weeks/tx
urgently/curable)

-Histo: sheets of lg lymphos

Immunodeficiency-assoc large B cell Lymphoma
-Acquired (HIV, post-transplant, inherited)
-oftern arise fromB-cells latently infected with EBV
-often involve the brain (esp HIV+ cases)
Burkitt's

Highly Agressive
(days/Tx
emergently/curable)

-African (endemic), Sporadic (non endemic)

-t(8; 14), MYC (Promoter) + Ig promoter = v. rapid growth
-EBV (esp African)
-Starry sky appearance on histo, very chemo sensitive!

Hodgkins vs. Non-Hodgkins lymphoma

Hodgkin's lymphoma

Non-Hodgkin's Lymphoma

Often Single lymph node or group of LN

Contiguous spread
Extra-nodal rare
Bimodal distribution: YA and >55yrs
B symptoms: high fever, drenching night
sweats; weight loss >10%

Multiple LN sites
Non-contiguous spread
Extranodal v. common
Peak age 20 - 40yrs
fewer signs/Sx

Genetic Alterations in Cancers

Genetic Alteration
Inc c-myc
Inc bcl-2
BCR-ABL

Cancer

Genetic Mechanism

Burkitt Lymphoma
Follicular Lymphoma
Chronic Myelogenous
leukemia

t (8, 14) translocation

t (14, 18) translocation
t (9; 22) translocation

Others
Inc Her2/neu/ERB B2
Ras mutation
Loss of Rb

Breast cancer
various
retinoblastoma

p53 mutation
dec TCG-beta

various
colon cancer

Amplification
point mutation
deletion at 13q14 with
loss of heterozygosity
(LOH)
point mutation
point mutation