Myeloproliferative disorders
Diseases of the bone marrow and
blood
In myeloproliferative diseases, a
greater than normal number of
blood stem cells develop into one
or more types of blood cells and
the total number of blood cells
slowly increases
 In myeloproliferative disorders,
cells mature normally, but they
have an abnormally high amount
of proliferation – hence the name
emphasizes they are proliferative.
This can lead to very high numbers
of cells in the blood.
Signs and symptoms
 Shortness of breath during
exertion
 Weakness and fatigue
 Pale skin
 Loss of appetite
 Prolonged bleeding from
minor cuts due to low
platelet counts
 Purpura, a condition in
which the skin bleeds,
causing black and blue or
pin-sized spots on the skin
 Sinus, skin or urinary
infections due to low white
blood cell counts
Cause Cause
 chromosome negative cases  Exposure to chemotherapy
have an
activating JAK2 or MPL mut
ation
Myelodysplastic syndromes
 conditions that can occur when the blood-
forming cells in the bone marrow become
abnormal
In myelodysplastic diseases, the blood stem
cells do not mature into healthy red blood
cells, white blood cells, or platelets and as a
result, there are fewer of these healthy cells
 In myelodysplastic syndromes, the cells
mature abnormally. A stem cell in the bone
marrow, instead of maturing into a normal
cell, matures into something else –
something just weird, and often not very
functional
Signs and symptoms
 Anemia (low RBC count or
reduced hemoglobin) – chronic
tiredness, shortness of breath, chilled
sensation, sometimes chest pain
 Neutropenia (low neutrophil count) –
increased susceptibility to infection
 Thrombocytopenia (low platelet
count) – increased susceptibility
to bleeding and ecchymosis (bruising
), as well as
subcutaneous hemorrhaging resulting
in purpura or petechiae
 Splenomegaly or
rarely hepatomegaly
(especially alkylating agents such
as melphalan, cyclophosphamide, bu
sulfan, and chlorambucil)
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  Mutations in CALR have
been found in the majority
of JAK2 and MPL-negative
essential thrombocythemia
and myelofibrosis
Diagnosis
Thrombocythemia
 Sustained platelet counts
greater than or equal to
600x109/L
 Bone marrow biopsy
showing proliferation
mainly in the megakaryocyte
line with enlarged, mature
megakaryocytes.
Myelofibrosis
 Varying degrees of fibrosis
in the bone marrow
 Leukoerythroblastosis, often
with significant dysmorphic
features in all three cell lines
 Splenomegaly, and often
hepatomegaly, secondary to
extra medullary
hematopoiesis.
 The blood findings include
prominent anisocytosis and
poikilocytosis in the red
blood cells, with teardrops
(dacrocytes)  fresh specimen, since live cells are
 Nucleated red blood cells are
also frequently found
  A left shift in the white cell
series is typical, with
immature myeloid cells and
even occasional blasts.
Basophils are usually
increased. 
or radiation (therapeutic or
accidental).
 Xylene and benzene exposure has
been associated with myelodysplasia
 Atomic-bomb survivors 40 to 60
years after radiation exposure
Diagnosis
 Full blood count and examination
of blood film: The blood film
morphology can provide clues
about hemolytic anemia, clumping of
the platelets leading to
spurious thrombocytopenia,
or leukemia.
 Blood tests to eliminate other
common causes of cytopenias, such
as lupus, hepatitis, B12, folate, or
other vitamin deficiencies, kidney
failure or heart
failure, HIV, hemolytic
anemia, monoclonal gammopathy
 Flow cytometry is helpful to identify
blasts, abnormal myeloid maturation,
and establish the presence of
any lymphoproliferative disorder in
the marrow
 Cytogenetics or chromosomal
studies: This is ideally performed on
the bone marrow aspirate.
Conventional cytogenetics require a
induced to enter metaphase to allow
chromosomes to be seen
 Virtual karyotyping can be done for
MDS
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   Platelets are either normal
or decreased in number, and
often show dysmorphic
features, with giant platelets
and uneven or incomplete
granularity.
Polycythemia Vera
Major findings:
 increased RBC mass
 splenomegaly
 clonal genetic abnormality
other than Ph chromosome
or BCR/ABL fusion gene
 endogenous erythroid
colony formation in vitro
Minor findings:
 thrombocytosis >400 x 109/L
 WBC>12 x 109/L
 bone marrow biopsy
showing panmyelosis with
prominent erythroid and
megakaryocytic proliferation
 low serum erythropoietin
levels
Chronic myelogenous leukemia
 Peripheral basophilia greater
than 20%
 Persistent thrombocytopenia
(<100 x 109/L) unrelated to
therapy or persistent
thrombocytosis (>1000 x
109/L) unresponsive to
therapy;
 Increasing spleen size and
WBC count unresponsive to
therapy
 Cytogenetic evidence of
clonal evolution.

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 chronic myelogenous
leukemia (CML)
 polycythemia Vera 
 primary myelofibrosis (also
called chronic idiopathic
myelofibrosis) 
 Essential thrombocythemia 
 Chronic neutrophilic
leukemia
 Chronic eosinophilic
leukemia.

 Prostate cancer is cancer that occurs in the prostate — a small walnut-

shaped gland in men that produces the seminal fluid that nourishes and
transports sperm.
 Colorectal cancer (CRC), also known as bowel cancer, colon cancer,
or rectal cancer, is the development of cancer from the colon or rectum
(parts of the large intestine).

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