Leukemias: Pathology review

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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?  

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A 65-year old male, named Mike is admitted to the hospital for a lower respiratory tract infection.

He complains of easy bruising for the past months, and a few hours after admission, he rapidly deteriorates and starts to bleed from venipuncture sites.

Lab tests show low platelet count, and bleeding time, PT and PTT are prolonged.

Fibrinogen is decreased and d-dimers are elevated.

Peripheral blood smear shows schistocytes. Bone marrow biopsy shows more than 30% blast cells with Auer rods in the cytoplasm.

Next, there’s a mother with her 5-year old son, Luke.

Luke’s mother has noticed that he’s been less active and had recurrent upper respiratory tract infections in the past few months.

Clinical examination reveals diffuse lymphadenopathy. CBC shows anemia and leukopenia, while bone marrow biopsy shows more than 30% blast cells.

The last person is a 40-year old female, named Mia, who complains of recurrent upper respiratory tract infection, progressive fatigue, and abdominal fullness.

Clinical examination revealed severe splenomegaly. CBC shows anemia, increased WBCs, while blood smear shows increased granulocytes and immature forms of myeloid cells.

The lap score is low. Bone marrow biopsy shows blast count of 8%.

Okay, so all three people have leukemia.

Leukemias can occur when there’s uncontrolled proliferation of immature white blood cells.

The most immature type of cells are called blast cells, but sometimes cells near maturity that resemble normal white blood cells can also be affected.

Whatever the stage, these abnormal cells accumulate in the bone marrow or blood.

This differentiates them from lymphomas which can also arise from white blood cells, but they typically form solid tumors in lymphatic tissue such as lymph nodes, thymus, or spleen.

Leukemias are most commonly caused by genetic mutations.

These mutations can be chromosomal deletions, where part of a chromosome is missing; trisomies, where there’s one extra chromosome; and translocations, where two chromosomes break and swap parts with one another.

Regardless of the type of mutation, these abnormal cells can lead to a decreased levels of functional white blood cells, which weakens the immune system and results in increased susceptibility to infections.

Sources

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  4. "Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome" Cancer (2005)
  5. "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia" Blood (2016)
  6. "Childhood and adolescent cancer statistics, 2014" CA: A Cancer Journal for Clinicians (2014)
  7. "Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia" The Lancet Oncology (2000)
  8. "The peripheral blood in chronic granulocytic leukaemia. Study of 50 untreated Philadelphia-positive cases." Spiers AS, Bain BJ, Turner JE (1977)
  9. "iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL" Blood (2018)