Acute Promyelocytic Leukemia Workup

Updated: Jan 31, 2018
  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Laboratory Studies

The initial laboratory workup of acute promyelocytic leukemia (APL) should include a complete blood cell (CBC) count with differential, peripheral blood smear, comprehensive metabolic profile for baseline renal and liver function tests, electrolyte levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen measurements.


Other Tests

Many authorities recommend lumbar puncture at diagnosis of acute promyelocytic leukemia (APL) in high-risk patients (see Treatment, Medical Care) who present with a very high white blood cell (WBC) count. In these cases, the CNS may serve as a sanctuary site warranting intrathecal therapy. Coagulopathy should be corrected first, and lumbar puncture may sometimes be delayed until after induction therapy.

The cerebrospinal fluid (CSF), in addition to routine chemical and hematologic studies, should be cytospun and examined by a pathologist trained in examination of fluid cytospins. Flow cytometry of CSF should be done to look for the abnormal clonal cells.

Also, cardiac function should be examined by echocardiography or scintigraphy before the administration of anthracyclines.



A bone marrow biopsy with aspirate should be performed immediately. The sample should be sent for flow cytometry and cytogenetics. In addition, fluorescent in situ hybridization (FISH) for the translocation or reverse transcription–polymerase chain reaction (RT-PCR) for the PML-RAR alpha transcript should also be done. The typical phenotype of acute promyelocytic leukemia (APL) is myeloperoxidase positive and CD33 positive, human leukocyte antigen (HLA)-DR negative.


Histologic Findings

There are different morphologic variants of acute promyelocytic leukemia (APL), which include the following [12] :

  • The hypergranular subtype (classic M3) has frequent Auer rods, clumps of granular material containing lysosomes, peroxidase, lysosomal enzymes, and large crystalline inclusions (see Image 4 or below). Auer rods can be seen in other types of AML, but they are usually seen in acute promyelocytic leukemia (APL). The nucleus is folded or bilobed, and the cytoplasm contains prominent azurophilic granules. The bone marrow is usually hypercellular. The cells stain intensely for Sudan black and myeloperoxidase, but not for periodic acid-Schiff (PAS) and HLA-DR.
    Regularly hypergranular subtype of acute promyeloc Regularly hypergranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
  • The microgranular variant (M3v) also has a folded nucleus, but the cytoplasm has fine, dusky granules and Auer rods are rare. It is seen in 25% of cases of acute promyelocytic leukemia (APL).
  • The hyperbasophilic subtype shows an increased nucleocytoplasmic ratio and strongly basophilic cytoplasm with blebs. There are few granules and no Auer rods.
  • The last variant is PLZF-RAR alpha (M3r), and it has regular, condensed chromatin in the nucleus. There are fewer granules and rare Auer rods when compared with the hypergranular subtype.


The appropriate workup of acute promyelocytic leukemia (APL) should include a bone marrow biopsy and aspiration, with aspirate samples sent for flow cytometry, cytogenetics, and FISH for the usual translocations. The role of lumbar puncture and CSF examination is debated, but many authorities recommend CSF examination in patients who present with significant leukocytosis. The FAB classification system has been replaced by the WHO classification system. The FAB classification categorized leukemia based on cell morphology, including cytochemical stains, whereas the WHO system also includes flow cytometry, cytogenetic studies and, in some cases, clinical information.