Acute Prolymphocytic Leukemia (APL)

AML with t(15;17)

Epidemiology and Etiology:

· 5-8% of AML

Common sites:

·

Gross features:

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

• low: HLA-DR, CD34, CD11a, CD11b, CD18
• homogenous, bright: CD33
• heterogenous: CD13
• maybe: CD117
• weak or negative: CD15, CD65
• CD64 common
• Microgranular or bcr3 transcript: CD34, CD2 frequently
• CD56 (20%) associated with a worse outcome

Molecular features:

· t(15;17) producing the fusion gene RARalpha-PML which represses genes required for myeloid differentiation

· retinoic acid receptor alpha (RARA) on 17q12

· PML on 15q22

· Nuclear regulatory factor gene

· Q-RT-PCR is used to quantitate the amount of RARalpha-PML fusion transcript

· Can detect small amounts in early recurrence

· FLT3 point mutations (tyrosine kinase) (35-45%)

· Internal tandem duplication (FLT3-ITD)

· Most common

· Higher WBC count

· Microgranular blast morphology

· Involvement of bcr3 breakpoint

· Tyrosine kinase domain mutations (FLT3-TKD)

· results in its constitutive activation

· secondary cytogenetic changes (40%) (no impact on prognosis):

· +8 (10-15%)

· del(7)(q*)

· del(9)(q*)

· ider(17)(q10)t(15;17)

· +21

· ~1% have fusion proteins involving other genes fused to RAR-alpha (“AML with a variant RARA translocation”)

· most still respond to ATRA

· ZBTB16 (previously PLZF) at 11q23

· Resistant to ATRA

· Predominance of hypergranular cells with regular nuclei

· absence of Auer rods usually

· increased number of Pelgeroid neutrophils

· strong MPO activity

· NUMA1 at 11q13

· Nuclear matrix associated gene

· NPM1 at 5q35

· Nucleophosmin gene

· Responds to ATRA

· STAT5B at 17q11.2

· Resistant to ATRA

·

Other features:

· Additional cytogenetic changes have no impact on prognosis

References:

· Swerdlow. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. 4th ed. WHO Publications; 2008.

· Heim & Mitelman. Cancer Cytogenetics, 3^rd ed. (2009)