Acute Leukemias Flashcards
what is causing the increase in WBC count in acute leukemia?
overproduction of blast cells (immature) which are nonfunctional
(>20% of blasts in bone marrow, vs normal of <5%)
the challenge of identifying acute leukemia is that the earlier the blasts are, the harder it is to tell them apart.
what can be used to distinguish between myeloid lineage cells from lymphoid lineage cells in histological imaging?
granule contents can identify myeloid lineage cells (blasts)
azurophilic granules (primary) contain myeloperoxidase (MPO), ONLY found in myeloid cells
[also detection of Auer Rods - fused azurophilic granules]
what is an Auer rod and what does it indicate (histological imaging)?
Auer rod is fusion of azurophilc (primary) granules - indicate cell of MYELOID lineage (blast)
what do lymphoblasts express uniquely that can be used to identify lymphoblasts vs myeloidblasts in acute leukemia?
lymphoblasts express DNA polymerase Terminal deoxynucleotidyl transferase (TdT)
incorporates nucleotides in template-independent manner using ssDNA, essential to VDJ recombination
requires staining for TdT or detection via flow cytometry
in acute leukemia, a large amount of nonfunctional leukemic blasts fill the bone marrow
what is the consequence of this? include how patients will present
leukemic blasts suppress normal hematopoiesis
present with pancytopenia:
- anemia: fatigue, tachycardia, flow minor, pallor
- thrombocytopenia: bruising, bleeding, new rash, petechiae, purpura
- neutropenia: fever, infection (pulmonary - pneumonia)
which is more common in adults and children, respectively?
acute lymphoblastic leukemia
acute myeloblastic leukemia
children: acute lymphoblastic (85%), of of these mostly pre-B cell (85%) vs pre-T cell
adults: acute myeloblastic leukemia
most common cancer in children
acute lymphoblastic leukemia: malignant proliferation of lymphoblasts, two types:
1. pre-B cell (85%), bone marrow and blood
2. pre-T cell (15%), thymic mass
*note 10-20x increase risk of both lymph/myeloidblast leukemia with Down syndrome
what are the clinical features of B cell ALL (acute lymphoblastic leukemia)?
*most common cancer in children
fatigue, fever, bone pain (due to expanding bone marrow mass), arthralgia (joint pain)
low Hb/Hct/platelet, WBC with blasts on peripheral smear
leukemic cells can infiltrate tissues —> palpable liver/spleen, enlarged lymph nodes, testicular enlargement, CNS infiltration to meninges
what are 3 important pieces of diagnosing B-ALL (acute lymphoblastic leukemia)?
- bone marrow biopsy (high nuclear to cytoplasmic ratio)
- identify cell type - B vs T, absence of myeloid differentiation (no myeloperoxidase granule staining), cytogenics
- examine CSF (for meninge infiltration)
what are the important cell surface markers that would help identify a pre-B ALL vs pre-T ALL?
both B and T cells are TdT+
B lymphoblast markers:
CD10
CD19
CD20 (late)
what is the significance of a t(12;21) translocation in children?
t(12;21): ETV6-RUNX1 (TEL-AML1) translocation
translocation of transcription factors that normally regulate cell growth in hematopoiesis, causes B cell ALL (acute lymphoblastic leukemia)
good prognosis if this is present
when does acute pre-T cell leukemia/lymphoma typically occur?
~age 15, when the thymus is reaching its peak size in development
can lead to compression (airway, vascular - Superior Vena Cava syndrome)
what do T lymphoblasts express that would help differentiate a pre-T ALL vs pre-B ALL?
both B/T cells are TdT+
T lymphoblasts express CD3, CD5, CD7 (CD4 and CD8 late)
what is the mean age of onset for acute myeloid leukemia in adults? is it more common in females or males?
more common males, 65-70
what is the clinical presentation of AML (acute myeloid leukemia)?
fatigue, weight loss
organ infiltration only with monoblast lineage - gums, chloromata/ granulocytes sarcoma (skin)
bone marrow replacement—> anemia, thrombocytopenia, neutropenia
leukostasis (WBC over 100K)
