Page 55 - Read Online

infiltration (EMI) is fairly common in AML patients. In Acute promyelocytic leukemia (APL) is another subtype
addition, MS has been observed in all age groups, and may of AML defined as having a translocation between
occur anywhere in the body. The most common tissues chromosomes 15 and 17 and generation of promyelocytic
include soft tissues, bone, peritoneum, lymph nodes and leukemia/retinoic acid receptor alpha fusion protein.
[16]
gastrointestinal tract. Other occasional sites include male This fusion protein causes a block at the promyelocytic
and female urogenital system and central nervous system differentiation stage. APL can occur in extramedullary
[17]
(CNS). Moreover, several studies have found a worse form, and EMI is responsible for 3-8% of cases in relapse.
[7]
prognosis in cases of acute leukemia with EMI, which The most common target tissues are CNS and skin.
[18]
may be explained by a poor response to chemotherapy Some studies indicate a relationship between 11q23
and disease relapse. Evaluation of the cellular and mixed-lineage leukemia rearrangement (MLLr) and EML.
[8]
molecular structures of extramedullary niches, as well According to some studies, the involvement in this type
as the migration and homing of leukemic cells, may help of cytogenetic abnormalities has been limited to chest and
in designing diagnostic and therapeutic techniques and uterus. [19,20] Furthermore, another study suggests a link
preventing relapse. However, there is still little information between MLLr and lymph node involvement. More
[21]
in this regard. The aim of this study was to investigate the studies are needed to confirm these observations.
characteristics of leukemic cells and the changes in their
microenvironment that promote to EMI. Molecular abnormalities associated with EML have not
been systematically defined; however, a well-documented
GENETIC AND MOLECULAR FEATURES molecular abnormality is a mutation in the nucleophosmin
OF EXTRAMEDULLARY INFILTRATION (NPM-1) gene. Nucleolar phosphoprotein or NPM-1 is
[12]
IN AML localized in nuclear foci and is a multifunctional protein
expressed in various cells. NPM-1 gene mutation is the
[22]
Extramedullary leukemia (EML) is also called MS, most common molecular genetic abnormality in AML,
[23]
granulocyte sarcoma and chloroma. In the WHO particularly AML with normal karyotype. NPM-1 is
[24]
classification, MS is an important subgroup of myeloid mutated in almost 15% of cases of MS. In a survey
neoplasia and acute leukemia. MS may occur simultaneously conducted on 89 AML patients, 15 patients (18%) had
with, before or after the diagnosis of AML. Genetic extramedullary manifestation at diagnosis, and 13 of them
[9]
mutations and molecular aberrations are an important tool (87%) had mutated NPM-1. [25]
for the evaluation of acute leukemia and assessment
of prognosis. However, there is very limited information FMS-related tyrosine kinase 3-internal tandem duplication
on the role of genetic mutations in MS. Although the (FLT3-ITD) mutation is observed in 28-34% of cases
[10]
overall incidence of MS in AML has been reported at of AML with normal cytogenetics. It plays an important
1.4-9%, it is particularly high in some subtypes of AML, role in cell proliferation, survival and differentiation of
[26]
reaching 18-24% in AML patients with t(8:21) and 25% hematopoietic progenitor cells. Some studies have
in pediatric AML. Other genetic abnormalities diagnosed found an association between FLT3-ITD mutation and
[11]
in EML patients include t(15:17), t(9:11), t(1:11), t(8:17), EML, so that in one study, 15% of MS patients have this
del(16q), del(5q), del(20q), monosomy 7, trisomy 4 and mutation. [27,28]
trisomy 8. Moreover, according to the French-American-
[12]
British classification, some AML types are associated with CD56, a neural cell-adhesion molecule, is expressed in
EML, including M4 and M5 monocytic leukemias and the normal, natural killer cells. Aberrant expression of CD56
M2 subtype. [13] in AML blasts, particularly AML with translocation t(8:21)
correlates with a worse prognosis than CD56-negative
[29]
The t(8:21) has been reported as the most common cases. An association has been described between the
cytogenetic abnormality associated with EML, occurring expression of CD56 and EMI, especially in lymph nodes
both at presentation and upon relapse, and is associated (lymphadenopathy). [21,30,31] CD56 gene is in the 11q23.1
with orbital involvement in infants. Inv(16) is another locus. Due to this fact and to the connection between
[32]
[10]
abnormality associated with EML; it is rarer than t(8:21). 11q23 mutation and EMI, MLLr is likely associated with
According to studies, the bowel may be a target organ aberrant expression of CD56 in EMI. Some case reports
in men with inv(16) while breast and ovary tend to develop and studies support this hypothesis. [20,21,33]
EML in female patients with inv(16). AML with trisomy
[14]
8 is found in nearly 5% of AML cases with a genetic Minimal residual disease (MRD) assessment is an important
abnormality. According to a study, trisomy or tetrasomy of feature of therapy management, especially in cases whose
chromosome 8 is observed in 35-65% of AML cases with recurrence risk is high. There is not much information on
leukemia cutis as a type of MS. Although confirmation MRD in MS patients, and only one study has evaluated
of this relationship requires further evaluation, based on the correlation between continuous detection of AML1-
numerous reports, we can suggest that trisomy 8 is a risk MTG8 chimeric transcripts in BM and peripheral blood,
factor for skin infiltration in AML. [15] and extramedullary relapse in t(8:21) AML. [34]

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ Issue 2 ¦ February 29, 2016 ¦ 45