Leukemia acute
Recurrent genetic abnormalities
Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARα



Topic Completed: 1 February 2013

Revised: 15 November 2019

Revised: 17 January 2019, last major update February 2013

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PubMed Search: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12)


Syed Zaidi, M.D.
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Cite this page: Zaidi S. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARα. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaAPL.html. Accessed November 17th, 2019.
Definition / general
  • Either hypergranular (this section) or microgranular / hypogranular
  • 5 - 8% of AML cases
  • Formerly called AML M3
  • Median age 35 - 40 years but can occur at any age
  • Decreased WBC count (hypergranular variant) at presentation with abnormal promyelocytes
  • Usually disseminated intravascular coagulation (DIC) and hemorrhage before or during induction chemotherapy, which may cause early death
  • Rarely organomegaly, extramedullary disease, skin involvement (detect with FISH, Mod Pathol 2005;18:1569)
  • Criteria for diagnosis: most cells (> 50%) are abnormal promyelocytes with heavy cytoplasmic granulation that may obscure the nuclear cytoplasmic margin, often reniform or bilobed nucleus; cells with multiple Auer bodies usually present; also bundles of Auer rods ("faggot cells" - resembles bundle of sticks)
  • Note: if t(15;17) present, diagnose as AML even if initial blast count is < 20%
Prognostic factors
  • In children, age < 10 years is favorable (Cancer 2006;106:2495)
  • Survival: excellent if DIC and hemorrhage are adequately controlled; excellent in adults with complete remission
Treatment
  • Combination chemotherapy required for sustained remissions (Hematology Am Soc Hematol Educ Program 2006:147)
  • All trans retinoic acid (ATRA) causes neoplastic promyelocytes to rapidly differentiate into bizarre maturing neutrophils, but patients eventually relapse
  • Arsenic trioxide (ATO) for ATRA-refractory patients; induces differentiation at low doses, marrow necrosis at high doses (Mod Pathol 2000;13:954)
Microscopic (histologic) description
  • Most cells are hypergranular promyelocytes (abundant cytoplasm, round / oval and frequently eccentric nuclei with occasional clefts or indentations, moderately condensed chromatin and indistinct nucleoli) with heavy red / purple cytoplasmic granulation that may obscure nuclear borders
  • 90% have multiple Auer rods in some cells, which may resemble bundles of sticks
  • Reniform (kidney shaped) nucleus; may have basophilic cytoplasm, < 20% myeloblasts
  • Post-treatment: may be difficult to differentiate residual disease (promyelocytes not in any particular location) from regenerating marrow (promyelocytes are perivascular and endosteal)
Microscopic (histologic) images

Bone marrow smears (Wright-Giemsa):
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Abundant azurophilic granules;
2 microgranular promyelocytes
with basophilic cytoplasm
and lobulated nuclei



Bone marrow biopsy:
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Bone marrow is almost completely replaced by promyelocytes
with abundant cytoplasm, oval / round nuclei that are often
eccentrically located, with occasional indentations / clefts,
somewhat condensed chromatin and indistinct nucleoli

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Promyelocytes are relatively uniform
with abundant cytoplasm containing dense
azurophilic granules and multiple Auer
rods, nuclei are round, oval and lobulated



Treatment related:
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Post-chemotherapy smear
shows cell with numerous
Auer rods in bundles



Images hosted on other servers:

Bone marrow smears (Wright-Giemsa):
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Abundant azurophilic granules



Stains:
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CD99 (figures 3C/3D)

Positive stains
Negative stains
Molecular / cytogenetics description

Table 3: cytogenetic abnormalities in APL (eMedicine: Acute Myeloid Leukemia (AML) Workup [Accessed 2 April, 2018]):

Translocation    Genes Involved    All-Trans-Retinoic Acid Response
t(15;17)(q21;q11) PML/RARα      Yes
t(11;17)(q23;q11) PLZF/RARα      No
t(11;17)(q13;q11) NuMA/RARα    Yes
t(5;17)(q31;q11)   NPM/RARα     Yes
t(17;17)     stat5b/RARα    Unknown

Molecular / cytogenetics images

Images hosted on PathOut server:
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t(15;17) - arrowheads at breakpoints
on abnormal chromosomes

Electron microscopy description
  • Auer rods have tubular substructure, markedly dilated endoplasmic reticulum and stellate complexes of rough ER
  • Nucleus has dispersed chromatin and prominent nucleolus
Electron microscopy images

Images hosted on PathOut server:
Missing Image

Cytoplasm has numerous dense
granules and several Auer rods,
nucleus has dispersed chromatin
and prominent nucleolus

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Cross section of Auer
rod shows characteristic
tubular structure

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