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Leukemia - Acute

Recurrent genetic abnormalities

Acute promyelocytic leukemia - therapy related


Reviewer: Syed Zaidi, M.D. (see Reviewers page)
Revised: 17 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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● Not a WHO diagnosis
● Prior tumor is usually breast carcinoma, other solid tumor or non-Hodgkin’s lymphoma treated with radiation or chemotherapy (J Clin Oncol 2003;21:2123)
● Usually develops within 3 years, with no preleukemic phase

Pathophysiology
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● Mitoxantrone, etoposide or their metabolites stimulate topoisomerase II to cleave different sites in PML and RARA, which are then translocated (N Engl J Med 2005;352:1529)


Breakpoint Hot Spot in PML Intron 6 in Mitoxantrone-Related APL

Case reports
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● 8 year old girl with secondary APL post chemotherapy for non Hodgkin lymphoma (J Pediatr Hematol Oncol 2004;26:427)
● 47 year old woman with therapy-related APL after radioactive iodine for thyroid cancer (J BUON 2007;12:129)
● 69 year old woman with microgranular APL post-chemotherapy for breast cancer (Cancer Genet Cytogenet 2002;138:143)

Micro description
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● Classic findings of APL plus dyserythropoiesis and dysmegakaryopoiesis

Molecular description
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● t(15;17)(q22;q12), often with additional abnormalities
● PML-RARa in most cases; FLT-3 gene mutations in 42% (Am J Clin Pathol 2005;123:840)

End of Leukemia - Acute > Recurrent genetic abnormalities > Acute promyelocytic leukemia - therapy related


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