Chronic leukemia

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Chronic leukemia

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A 60-year-old man comes to the office because of progressive weakness and a dragging sensation in the abdomen for the past 3 months. The patient is a retired farmer. Past medical history is noncontributory. He does not smoke or use illicit drugs. Temperature is 37.0°C (98.6°F), pulse is 96/min, respirations are 20/min, and blood pressure is 125/80 mmHg. Physical examination shows mucosal pallor, petechiae on the lower extremities, and splenomegaly crossing the midline. Laboratory results are as follows:  
 
 Laboratory value  Result 
 Complete blood count 
 Hemoglobin   9.3 g/dL 
 Platelets   70,000/mm3 
 Leukocytes   6,000/mm3 
Peripheral blood smear is shown:


Reproduced from:Wikimedia Commons 

Which of the following genes is most likely to be mutated in this patient?  

External References

First Aid

2024

2023

2022

2021

“Blast crisis p. 437

Blast crisis in CML p. 733

Chronic myelogenous leukemia (CML) p. 437

age ranges p. 733

basophilia caused by p. 414

busulfan for p. 444

chromosomal translocations and p. 439

imatinib for p. 445

oncogenes and p. 220

Philadelphia chromosome p. 733

Transcript

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With chronic leukemia, “leuk” refers to white blood cells, and “emia” refers to the blood; so in chronic leukemia there are lots of partially developed white blood cells in the blood over a long period of time.

These partially developed white blood cells interfere with the development and function of healthy white blood cells, platelets, and red blood cells.

Now, every blood cell starts its life in the bone marrow as a hematopoietic stem cell.

Hematopoietic stem cells are multipotent -- meaning that they can give rise to both myeloid or lymphoid blood cells.

If a hematopoietic stem cell develops into a myeloid cell, it’ll mature into an erythrocyte -- or a red blood cell, a thrombocyte -- or a platelet, or a leukocyte -- or a white blood cell, like a monocyte or granulocyte.

Granulocytes are cells with tiny granules inside of them -- they include neutrophils, basophils, and eosinophils.

If a hematopoietic stem cell develops into a lymphoid cell, on the other hand, it’ll mature into some other kind of leukocyte: a T cell, a B cell, or a natural killer cell, which are referred to as lymphocytes.

Once the various blood cells form, they leave the bone marrow, and travel around the blood, or settle down in tissues and organs like the lymph nodes and spleen.

Chromosomal abnormality in hematopoietic stem cells that are destined to become leukocytes is the most common cause of chronic leukemia.

Some examples of abnormalities include a chromosomal deletion, where part of a chromosome is missing, a trisomy, where there’s one extra chromosome, and a translocation, where two chromosomes break and swap parts with one another.

Now there are two types of chronic leukemia.

The first is chronic myeloid leukemia, CML, which is caused by a particular chromosomal translocation that affects granulocytes.

The second is chronic lymphocytic leukemia, CLL, which is caused by a variety of chromosomal mutations that affect lymphocytes, in particular B cells.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future" Cells (2021)
  6. "Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future" Cells (2021)
  7. "Pathogenesis of chronic lymphocytic leukemia and the development of novel therapeutic strategies" Journal of Clinical and Experimental Hematopathology (2020)
  8. "Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management" American Journal of Hematology (2019)
Elsevier

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