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u world usmle step 1 biochemistry (part 2) question bank
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1. A 67-year-old man comes to the physician complaining of pallor,early satiety, and severe fatigue. He has also lost 20 pounds (9.07
kg) over the past 6 months. Physical examination reveals
hepatomegaly and massive splenomegaly. A cytosolic protein
recovered from his white blood cells is found to have constitutive
tyrosine phosphorylation activity. Consequently, there is persistent
activation of STAT (signal transducers and activators of
transcription)proteins. The patient is most likely suffering from
which of the following disorders?
A. Acute lymphocytic leukaemia
B. Acute promyelocytic leukaemia
C. Chronic lymphocytic leukaemia
D. High grade non-hodgkin’s lymphoma
E. Myelofibrosis
Answer: E
Explanation:
Chronic myeloproliferative disorders
Disorder Diagnostic features Mutation
Chronic myelogenous Constitutional Philadelphia
leukaemia symptoms(eg. chromosome t(9:22)
Fatigue,weight BCR-ABL fusion
loss,excessive protein
sweating),
splenomegaly &
leukocytosis with
marked left shift (eg.
myelocytes,metamyel
ocytes, band forms)
Essential Hemorrhagic and JAK2
thrombocytosis thrombotic
symptoms(eg. Easy
bruising,
microangiopathic
occlusion),
, thrombocytosis &
megakaryocytic
hyperplasia
Polycythemia vera Pruritus,erythromelalgi
a,splenomegaly,
thrombotic
complications,erythroc
ytosis &
thrombocytosis
Primary myelofibrosis Severe
fatigue,splenomegaly
(often causing early
satiety/abdominal
discomfort),
hepatomegaly,
anaemia & bone
marrow fibrosis
The chronic myeloproliferative disorders are a group of bone marrow
diseases characterised by the overproduction of myeloid cells. Primary
myelofibrosis is caused by atypical megakaryocytic
hyperplasia. The clonally expanded megakaryocytes activate fibroblast
proliferation, resulting in progressive replacement of the marrow space
by extensive collagen deposition. In the early stages, there is marrow
hypercellularity with minimal fibrosis. As the disease progress,
pancytopenia can result. Hepatomegaly and massive splenomegaly
occur in myelofibrosis because the loss of bone marrow hematopoiesis
is compensated for by extramedullary hematopoiesis. The peripheral
smear characteristically shows teardrop- shaped red blood cells
(dacrocytes) and nucleated red blood cells.
,(Choice C) Chronic lymphocytic leukaemia is a lymphoproliferative
disorder involving B-lymphocytes. With the exception of chronic
myelogenous leukaemia, the chronic myeloproliferative disorders
(especially polycythemia vera) frequently harbour a mutation in the
cytoplasmic tyrosine kinase, Janus kinase 2(JAK2). This mutation
(V617F) substitutes a bulky phenylalanine for a conserved valine at
position 617, resulting in constitutive tyrosine phosphorylation activity,
and consequently, cytokine-independent activation of the JAK-STAT
pathway. A JAK2 inhibitor (ruxolitinib) has been approved for the
treatment of primary myelofibrosis.
(Choice A) Acute lymphocytic leukaemia predominantly affects children.
Clinical manifestations are nonspecific and include fever, fatigue, pallor,
petechiae, and bleeding. Leukemic spread can cause lymphadenopathy,
hepatosplenomegaly, and bone pain.
(Choice B) In acute promyelocytic leukaemia, the translocation t(15;17)
leads to the formation of a fusion gene between the promyelocytic
leukaemia (PML} and the retinoic acid receptor alpha (RARa) genes.
This abnormal PML/RARa fusion protein blocks the differentiation of
myeloid precursors.the most significant laboratory finding is marked
lymphocytosis, with "smudge cells" seen on peripheral blood smears.
The majority of cases exhibit increased expression of the proto-
oncogene BCL-2,similar to follicular lymphomas.
(Choice D) Several high-grade non-Hodgkin lymphomas are associated
with cytogenetic abnormalities. The t(8;14) translocation is the most
common in Burkitt lymphoma and involves the c-myc oncogene. Burkitt
lymphoma is associated with Epstein-Barr virus infection and classically
has a "starry sky" histologic appearance.
, 2. A 72-year-old Caucasian female presents to your office
complaining of difficulty in swallowing. She also complains of
severe fatigue and progressive exertional dyspnea. Physical
examination reveals pale conjunctiva. A photograph of her finger is
shown below.
Which of the following is the best treatment for this patient?
A. Iron preparations
B. Vitamin B12
C. Pyridoxine
D. Vitamin C
E. Folic acid
F. Erythropoietin
G. Filgrastim
Answer: A
Explanation:
Many clinical features that occur due to decreased haemoglobin are
common for all types of anaemia. These features include malaise,
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