AJCP / Original Article

Aberrations of MYC Are a Common Event in B-Cell

Prolymphocytic Leukemia
Ellen Flatley, MD,1 Andy I. Chen, MD,2 Xiangrong Zhao, MD, PhD,3 Elaine S. Jaffe, MD,3
Jennifer B. Dunlap, MD,1 Stefania Pittaluga, MD, PhD,3 Shahed Abdullah,3 Susan B. Olson, PhD,4
Stephen E. Spurgeon, MD,2 and Guang Fan, MD, PhD1

From the 1Department of Pathology, Oregon Health & Science University, Portland; 2Department of Hematology-Oncology, Knight Cancer Institute,
Oregon Health & Science University, Portland; 3Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute,
Bethesda, MD; and 4Knight Diagnostic Laboratory, Knight Cancer Institute, Oregon Health & Science University, Portland.

CME/SAM
Key Words: Leukemia; MYC; Prolymphocytic leukemia; Cytogenetics; FISH

Am J Clin Pathol September 2014;142:347-354

DOI: 10.1309/AJCPUBHM8U7ZFLOB

ABSTRACT Upon completion of this activity you will be able to:

Objectives: B-cell prolymphocytic leukemia (B-PLL) remains
a controversial entity, and its molecular pathogenesis
is largely unknown. Patients are older, typically having
marked lymphocytosis and splenomegaly in the absence of
lymphadenopathy. It is defined as a mature B-cell leukemia
with more than 55% circulating prolymphocytes. Leukemic
mantle cell lymphoma and chronic lymphocytic leukemia in
prolymphocytic transformation must be excluded.
Methods: Case archives were retrospectively reviewed for
B-PLL in patients without a previous diagnosis of chronic
lymphocytic leukemia or other B-cell neoplasm.
Results: We identified six cases of B-PLL with available
cytogenetic data, five of which showed evidence of
aberrations in MYC. Three cases showed additional signals
for the MYC gene by fluorescence in situ hybridization
(FISH), and two cases demonstrated t(8;14)MYC/IGH by
karyotyping or FISH. High levels of MYC protein expression
were detected in all cases tested with MYC aberrations.
Conclusions: These results suggest that deregulation of
MYC plays an important role in the pathogenesis of B-PLL
and expands the spectrum of B-cell neoplasms associated
with aberrations of MYC.
• define diagnostic criteria for B-cell prolymphocytic leukemia (B-PLL).
• list differential diagnoses for B-PLL.
• discuss the mechanism of MYC deregulation in B-cell lymphoma.
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B-cell prolymphocytic leukemia (B-PLL) is a rare,
aggressive B-cell malignancy, with limited knowledge
currently available regarding its molecular pathogenesis. It
is categorized by the World Health Organization as a mature
B-cell neoplasm in which prolymphocytes comprise greater
than 55% of circulating lymphoid cells.1 Morphologically,
prolymphocytes are medium to large in size with an
ample basophilic cytoplasm and round to oval nuclei
containing clumped chromatin and prominent nucleoli.
Chronic lymphocytic leukemia (CLL) in prolymphocytic
transformation can show similar morphologic features.
Mantle cell lymphoma in the leukemic phase can show
some similar features but is distinguished by the presence
of the t(11;14).2
Patients with B-PLL are typically adults in the
seventh decade who have B symptoms and splenomegaly.
Lymphadenopathy is uncommon. Peripheral blood shows
a markedly increased lymphocyte count, accompanied by
anemia and thrombocytopenia in about 50% of cases.1

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347 DOI: 10.1309/AJCPUBHM8U7ZFLOB 347
Flatley et al / MYC in B-Cell Prolymphocytic Leukemia
Cytogenetic studies and molecular profiling have failed
to show a single defining genetic aberration, but complex
karyotypes,3 abnormalities of TP53/p53,4 deletions at
11q23, deletions at 13q14, and trisomy 12 have been
reported.5 A small number of reports have shown MYC
translocations, including t(8;14), in transformed CLL and
B-PLL.6-9 Put et al6 found MYC rearrangement in nine
cases originally reported as B-PLL gathered from multiple
centers; however, four of nine had a CLL-like phenotype
(CD5+/ CD23+), favoring transformed CLL rather than de
novo B-PLL. One study used gene expression profiling to
compare de novo B-PLL with CLL and found increased
expression of MYC to be a distinguishing feature.10
However, the basis of MYC overexpression has not been
fully explored. Therefore, we undertook a study of cases of
B-PLL in which conventional cytogenetic or fluorescence
in situ hybridization (FISH) studies had been performed to
evaluate the status of the MYC gene. We identified three
cases with evidence of additional signals for MYC by FISH
and two cases with the t(8;14). To our knowledge, our
report is the first to identify B-PLL cases with increased
MYC signals by FISH and provides a new basis for
overexpression of MYC in this disease.
Materials and Methods
Cases
We retrospectively searched the case archives of the
Department of Pathology, Oregon Health & Science University
(OHSU), and the Hematopathology Section, Laboratory
of Pathology, National Cancer Institute (NCI), for cases of
B-PLL without a previous diagnosis of CLL or another B-cell
neoplasm. Six cases, in which the status of the MYC gene
had been investigated either by FISH or complete cytogenetic
karyotype, were identified. Five of the six cases had evidence
of aberrations involving MYC and comprise the subject of
this report. One patient diagnosed with B-PLL had a complex
karyotype lacking MYC abnormalities. This patient presented
to the emergency department with marked leukocytosis (37.9
× 103/µL) and hepatosplenomegaly and died of respiratory
failure within a few days of diagnosis. Clinical data were
provided by either the Department of Hematology-Oncology,
OHSU (cases 1, 2, and 4), or the referring clinicians from
original institutes (cases 3 and 5). Detailed information on
clinical follow-up was available for four of the five patients.
Approval was obtained from the institutional review boards at
OHSU and the NCI.
H&E-stained slides and Wright-Giemsa–stained smears
of peripheral blood and bone marrow smears were reviewed
by at least two of the authors for each case.
348 Am J Clin Pathol 2014;142:347-354
348 DOI: 10.1309/AJCPUBHM8U7ZFLOB
Immunohistochemistry Stains
Immunohistochemical staining on paraffin-embedded
tissue sections was performed according to previously
published methods.11 Accompanying flow cytometric data
were reviewed. For the anti–c-Myc rabbit monoclonal antibody
(Y69, 1:25 dilution; Abcam, Cambridge, MA), formalin-
fixed, paraffin-embedded (FFPE) sections were deparaffinized
in xylene, retrieved for 60 minutes using standard cell
conditioning, titrated, and incubated for 120 minutes at 37°C.
For the SOX11 mouse monoclonal antibody (MRQ-58, 1:50
dilution; Cell Marque, Rocklin, CA) stains, FFPE sections
were deparaffinized, rehydrated in graded alcohol, placed in hot
1× low-pH antigen retrieval solution (cat. no. S1699; DAKO,
Carpinteria, CA), and microwaved for 6 minutes. Sections were
blocked with Tris-goat (5%) solution and incubated for 120
minutes at room temperature. All sections were then detected in
the BenchMark XT with ultraView Universal DAB Detection
Kit (760-500; Ventana Medical Systems, Tucson, AZ) and
amplified using the Amplification Kit (760-080; Ventana
Medical Systems). MYC was considered positive if more
than 40% of tumor cell nuclei were positive, as determined
by comparison with CD20.12 SOX11 was scored as positive if
expressed in most tumor cells (>75%); negative cases did not
show any tumor cell reactivity.13
Cytogenetics
Conventional chromosomal analysis was performed on
cultured lymphocytes from peripheral blood or bone marrow
aspirate per standard procedures. For each case, metaphase
chromosomes from at least 20 cells were analyzed, and only
clonal aberrations were considered. FISH was performed
per standard procedures to characterize the aberrations of
MYC and, when applicable, its translocation partner.11 FISH
analyses with additional probes were also performed for cases
3 and 4 and excluded rearrangements of CCND1 as well as a
few other relevant gene loci. At least 200 interphase cells and
all probed metaphases were evaluated.
Results
All patients demonstrated significant leukocytosis
❚Table 1❚, splenomegaly, and bone marrow involvement,
while none presented with lymphadenopathy initially. The
morphologic features of the neoplastic cells from all cases
were characteristic of B-PLL. The circulating cells were
medium to large in size with prominent central nucleoli
❚Image 1❚. The chromatin pattern was generally coarsely
clumped and hyperchromatic. In Wright-Giemsa–stained
smears, the cytoplasm appeared basophilic but without
cytoplasmic vacuoles. Immunophenotypic analysis by flow
cytometry and/or immunohistochemistry ❚Table 2❚ revealed
© American Society for Clinical Pathology
 AJCP / Original Article

❚Table 1❚
Patient Clinical and Laboratory Features

    Blood                 Cytogenetics

WBC, Lymph % FISH

Case No. Age, y/Sex × 103/μL in PB Karyotypesa for MYC del(17p)

1 83/F 87 82 47,X,del(X)(q24q28),add(4)(q31), Three signals Yes

der(8)t(8;8)(p21;q24),del(9)(q13q22),
add(10)(q26),del(13)(q14q22),add(13)
(q14),add(14)(p11.2),del(17)(p11.2p13),
+19,add(22)(q13)[cp8]/47,sl,add(19)
(q13.4)[cp3]/47,sdl1,add(2)(p22)
[cp7]/46,XX[2]
2 65/M 262 96 NP More than five signals NP
3 72/M 22.9 64 44,XY,der(1)t(l;9)(p36.3;ql3),der(3)t(3;7) Three signals Yes
(pl3;q22),?del(6),(q21q22),der(7)del(7)
(q22) t(3;7)(pl3;q22),i(8)(ql0),der(9)t(l;9)
(p36.3;q13)t(9;l3)(ql3;qll.2),–13,del(17)
(p11.2),–18[cp12]/46,XY [8]
4 62/F 37.2 81 46,XX,t(8;14)(q24.1;q32)[2]/46,XX[19] MYC/IGH No
5 78/M 27.8 81 45,XY,add(6)(q27),add(7)(q32),del(7) MYC/IGH Yes
(q32),t(8;14)(q24.1;q32),–10,add(11)
(q25),der(12),add(12)(p13), hsr(12)
(p13),–13,add(14)(p10),–17,–18,del(20)
(q11.2), +1-3mar[4]/46,XY[16]

FISH, fluorescence in situ hybridization; NP, not performed; PB, peripheral blood.
a Boldface indicates aberrations of chromosome 8, where MYC is located.

that the neoplastic cells from all cases were positive for one or
more pan–B-cell markers while all were negative for CD23;
three of five cases also exhibited CD5 coexpression. Case
summaries are described below.
Case 1, Amplified MYC
An 83-year-old woman sought treatment for a several-
week history of progressive fatigue and had splenomegaly
(19 cm) without lymphadenopathy. She had a long-standing
history of monoclonal gammopathy of undetermined signifi-
cance, and repeat serum protein electrophoresis found an IgM
l M protein of 0.9 g/dL. She was also anemic (hemoglobin,
10 g/dL) with marked leukocytosis (87 × 103/mL) with 82%
lymphocytes.
Peripheral blood smear showed marked lymphocytosis
❚Image 2A❚. A bone marrow aspirate smear and biopsy speci-
men revealed hypercellular marrow with 90% involvement
by intermediate and some large atypical lymphocytes, with
minimal background trilineage hematopoiesis. The leukemia
cells were positive for CD5, CD19, CD20, and surface l light
chain. CD23, cyclin D1, and SOX11 were negative (Table 2).
High MYC protein expression was identified by immunohis-
tochemistry ❚Image 3❚.
Metaphase karyotyping revealed complex cytogenetics
(Table 1), which included deletion of 17p. FISH analysis
demonstrated the presence of an extra MYC signal in 67% of
cells ❚Image 2B❚ with two signals for the CEP8 centromere
probe and confirmed the deletion of the TP53 region.
The patient was treated with a combination of
corticosteroids, rituximab, and alemtuzumab. She had an
initial hematologic response but developed refractory disease
progression and died 1 month after diagnosis.
Case 2, Amplified MYC
A 65-year-old man sought care at an outside hospital
with marked lymphocytosis (WBC count, 262 × 103/mL)
with 96% lymphocytes, extensive bone marrow involvement,
and splenomegaly. The patient was treated initially with
rituximab, cyclophosphamide, vincristine, and prednisone
without response and then treated with fludarabine and
rituximab to a complete response.
He developed nodal disease 5 months later. Examination
of an epitrochlear lymph node revealed a diffuse monotonous
lymphocytic proliferation ❚Image 2C❚ with complete
effacement of nodal architecture and extension into perinodal
fat. The lymphoma cells were positive for CD5, CD20, and
c-Myc protein expression and negative for CD23, CD3,
CD10, cyclin D1, and SOX11. FISH testing with the MYC
break-apart probe demonstrated additional MYC signals, with
approximately 30% of counted cells containing three to four
MYC signals and 60% with more than five signals ❚Image 2D❚.
All cells had two signals with the CEP8 centromere probe.
He was treated with rituximab weekly for 4 weeks and
then received a reduced-intensity allogeneic transplant from
an unrelated donor. A posttransplant restaging marrow biopsy
specimen was negative for malignancy. The patient’s course
was complicated by pulmonary mucormycosis and graft-vs-
host disease of the gastrointestinal tract. The patient died of
these complications 4 months after transplant, 26 months
following his initial diagnosis.

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Flatley et al / MYC in B-Cell Prolymphocytic Leukemia

A B

C D

❚Image 1❚ Morphologic features of B-cell prolymphocytic leukemia. A, Peripheral blood smear shows marked lymphocytosis
(Wright-Giemsa; ×400). B, Circulating cells have features of prolymphocytes, with round to slightly irregular nuclei and prominent
central nucleoli. Cells have a rim of basophilic cytoplasm (Wright-Giemsa, ×1,000). C, Core biopsy specimen shows marked
hypercellularity with replacement of normal hematopoietic elements (H&E, ×400). Inset shows strong positivity for p53 in all
tumor cells (×400). D, Infiltrating prolymphocytes have prominent central nucleoli, and mitotic figures are observed (H&E, ×1,000).

Case 3, Amplified MYC
A 72-year-old white man sought treatment in 2012
with anemia (hemoglobin, 8 g/dL) and melena. He was
transfused to stable hemoglobin levels. WBC count was
22.9 × 103/mL with 64% lymphocytes. Further workup
revealed splenomegaly and liver cirrhosis, with no B
symptoms or lymphadenopathy per imaging studies.
Peripheral blood flow cytometric analysis was consistent
with B-cell leukemia. A subsequent bone marrow biopsy
specimen yielded a diagnosis of B-PLL. Accompanying
flow cytometric analysis of the marrow aspirate revealed
that 64% of lymphocytes were k-restricted B cells that
coexpressed CD5, CD11c, and CD43. The cells were
negative for CD23 and SOX11.
Conventional cytogenetic analysis revealed a complex
karyotype, including loss of the chromosome 17 short arm.
FISH analysis demonstrated an extra MYC signal in 44% to
46% of the nuclei and also detected the loss of BCL2 and
MALT1 signals, with no rearrangement of BCL2, CCND1,
IGH, MYC, or MALT1, and normal TP53 signals.
The patient was treated with chemotherapy, with the
WBC levels remaining elevated until 8 months of treatment
(18.9 × 103/mL); the most recent reported WBC level,
however, was within normal range (8 × 103/mL).

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 AJCP / Original Article

❚Table 2❚
Immunophenotype of B-Cell Prolymphocytic Leukemia

CD19/ c-Myc(+)/
Case No. CD20 CD5 CD23 Cyclin D1 SOX11 c-Myc CD20(+), % Ki-67, %

1 + + – – – + >90 70-80
2 + + – – – + >80 >90
3 + + – – – Unsatisfactory NA 40-50
4 + + – – – + >60 <30
5 + – – – – Not performed NA ~20

NA, not applicable due to unsatisfactory c-Myc result; –, negative; +, positive.

Case 4, Positive for t(8;14)(q24.1;q32)(MYC/IGH)
A previously healthy 62-year-old woman sought care
for weight loss and abdominal pain. She had splenomegaly
(26 cm) without lymphadenopathy. The patient was anemic
(hemoglobin, 8.9 g/dL), with marked leukocytosis (37.2 × 103/
mL) with 81% lymphocytes. A bone marrow biopsy specimen
was hypercellular (70%) with nodular and paratrabecular
infiltrates ❚Image 2E❚.
The prolymphocytes were positive for CD5, CD20,
Bcl-2, and c-Myc and negative for CD10, CD23, cyclin D1,
CD34, SOX11, and TdT. FISH was positive for a t(8;14)
MYC rearrangement ❚Image 2F❚, but no aberrations involving
BCL2, BCL6, or CCND1 were identified. Karyotype revealed
46,XX,t(8;14)(q24.1;q32)[2]/46,XX[19].
The patient was treated with dose-adjusted rituximab,
etoposide, prednisone, vincristine (Oncovin), and
hydroxydaunorubicin hydrochloride with intrathecal
methotrexate prophylaxis. She entered a complete remission
and was negative for minimal residual disease per flow
cytometric analysis. Her blood counts normalized, and she
remains in remission at the 2-year follow-up.
Case 5, Positive for t(8;14)(q24.1;q32)(MYC/IGH)
A 78-year-old man had leukocytosis (27.8 × 103/
mL), anemia (hemoglobin, 9.1 g/dL), mild splenomegaly,
no lymphadenopathy, and a history of idiopathic
thrombocytopenic purpura treated with corticosteroids and
intravenous immunoglobulin. Flow cytometric analysis of
peripheral blood showed that 81% of lymphocytes were
B cells, l restricted, and expressing CD19 (dim), CD79a
(cytoplasmic), CD10 (dim), FMC7, and HLA-DR. CD5,
CD23, and SOX11 were negative. The nuclei showed
strong expression of p53 by immunohistochemistry (Image
1C, inset). Conventional cytogenetic analysis revealed a
complex karyotype including t(8;14)(q24.1;q32) and loss
of chromosome 17 (Table 1). FISH analysis was positive
for MYC rearrangement. Bone marrow biopsy specimens
confirmed marrow involvement by a B-cell malignancy
consistent with B-PLL.
The patient was then treated with single-agent rituximab
and returned in 16 months with relapse as a right chest wall
subcutaneous nodule. A subsequent positron emission tomog-
raphy scan revealed widespread bony lesions. The patient
received radiation therapy and shortly after became paraple-
gic. The patient expressed a desire to be on comfort care only,
and no further therapy for his lymphoma was administered.
Discussion
MYC translocation or mutation is classically associated
with Burkitt lymphoma, but in recent years, aberrations in
MYC have been associated with an increasing number of
human malignancies, including other B-cell neoplasms, with
the prevalence estimated at 20%.14 Thus far, MYC aberrations
have been shown to occur as translocations, gene copy
number increase, and increased messenger RNA (mRNA)
accumulation. MYC is considered a global amplifier of the
transcriptional output of a particular cell type (lymphocytes,
embryonic stem cells, tumor cells, etc).15 MYC, considered
an oncogene, has a far-reaching network of influence; it is
thought to regulate the expression of more than 15% of all
cellular genes, affecting nearly all aspects of cellular activity.
Among the many genes it influences, most are involved
in cell growth, cell cycle progression, metabolism, protein
biosynthesis, apoptosis, and cell adhesion. The deregulation
of MYC therefore serves as a potential basis for tumorigenesis,
since it is involved in a number of proliferative activities.
We identified aberrations in MYC in a surprisingly high
percentage of cases of B-PLL, five of six cases tested. All five
patients had marked lymphocytosis, anemia, splenomegaly,
and marrow involvement, without initial lymphadenopathy or
a clinical history of CLL. CD23 was negative in all five cases,
but four of five cases expressed CD5. Two types of MYC gene
abnormality were seen, both increased MYC copy number
and MYC rearrangement. The three cases with increased copy
number showed a high Ki-67 expression level (40% to >90%)
and exhibited complex cytogenetic abnormalities (cases
1 and 3). Interestingly, both cases with t(8;14)(q24.1;q32)
translocation showed relatively low expression of Ki-67
(<30%). However, high MYC protein expression was seen
in all three evaluable cases, irrespective of the nature of

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Flatley et al / MYC in B-Cell Prolymphocytic Leukemia

A B

C D

❚Image 2❚ A, Peripheral blood smear from case 1 showing prolymphocytes (Wright-Giemsa, ×630). B, Fluorescence in situ
hybridization (FISH) for case 1 with MYC break-apart probe showing three intact signals consistent with a single increase in
copy number. C, Lymph node from case 2 showing cells with prominent nucleoli. D, FISH for case 2 on formalin-fixed, paraffin-
embedded tissue demonstrating at least four intact MYC signals in the plane of section.

the MYC aberration (Table 2). Interestingly, there was no
direct correlation between MYC expression and proliferative
activity, although the number of cases analyzed is small.
MYC abnormalities were often associated with TP53
deletion (del(17p)) in our series (three of four cases tested).
Recurrence as nodal disease was seen in one patient (case
2) with MYC amplification (more than five signals), and
recurrence as a subcutaneous mass was seen in another patient
(case 5) with MYC rearrangement.
A few case reports and small case series have found MYC
activating translocations in B-PLL, including de novo B-PLL
and CLL in prolymphocytoid transformation. Put et al6 reported
MYC rearrangement in nine cases originally diagnosed as B-PLL
from multiple institutions. However, they found a “CLL-like”
immunophenotype in four of nine cases and concluded that
they were more likely transformed CLL than de novo B-PLL.
None of our cases had clinical evidence of underlying CLL,
although CD5 was commonly expressed. B-PLL is a rare form
of B-cell malignancy, and in the past, some cases have been
proven to be examples of mantle cell lymphoma presenting
in the leukemic phase.2 We ruled out mantle cell lymphoma,
both by negative testing for cyclin D1 and negative staining for
SOX11. Furthermore, the hairy cell variant would be positive
for CD103 and usually positive for SOX11. Three of five cases
in this study were tested for CD103 by flow cytometry and
showed negativity, and all five were negative for SOX11 by
immunohistochemistry stain, as stated above. Thus, we think
the diagnosis of hairy cell variant is unlikely.

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E F
❚Image 2❚ (cont) E, Bone marrow aspirate from case 4 with prolymphocytic infiltrate (Wright-Giemsa, ×630). F, FISH for case 4
with tricolor dual-fusion probe demonstrating translocation of MYC and IGH by the presence of two fusion (yellow) signals in the
background of one IgH (green), one MYC (red), and two centromeres of chromosomes 8 (aqua) signals.
❚Image 3❚ B-cell prolymphocytic leukemia stained for MYC
protein (case 1) (×400). More than 90% of tumor cells
showed nuclear reactivity.
Reported translocations in B-PLL include t(8;14)MYC/
IGH, t(2;8)IGK/MYC, and t(8;22)MYC/IGL.8,9,16,17 MYC
translocations have occurred either as the sole cytogenetic
abnormality or in a background of complex karyotypes.
Activating translocations involve the juxtaposition of MYC
with constitutively active B-cell genes, most commonly IGH
on chromosome 14.
Gene expression profiling of B-PLL has shown
significant increases in MYC expression compared with
CLL. Specifically, Del Giudice et al10 subjected nine B-PLL
samples and 10 CLL samples to gene expression profiling.
© American Society for Clinical Pathology
AJCP / Original Article
Similar to our cases, most of the B-PLL cases (six of nine)
evaluated in this analysis also harbored TP53 abnormalities
(del(17p)). However, an increase in MYC copy number by
FISH, Ki-67, and clinical outcomes were not reported.
Another mechanism for MYC deregulation is an increase
in MYC copy number, including MYC amplification. MYC
amplification has been reported in cases of diffuse large B-cell
lymphoma, using FISH probes to demonstrate an increase in
MYC signals in comparison to the signals from centromeric
probes for chromosome 8. Furthermore, increased MYC
mRNA levels have been correlated with a copy number
increase, suggesting that increased copy number also may
portend an adverse prognosis.18
Here we report three B-PLL cases with increased MYC
copy numbers detected by FISH, varying from three to more
than five copies per cell. Two patients had a progressive
clinical course, and one patient had a 9-month follow-up.
While the exact prognostic value of the MYC copy number
increase in B-PLL is currently unclear, our small case series
suggests that an increase in MYC copy number on FISH
may be associated with poor clinical outcome, with similar
implications as the MYC translocation.
To our knowledge, there is no published association
between Ki-67 activity and MYC abnormality in B-PLL.
In a study of diffuse large B-cell lymphoma, there was no
association found between MYC copy number and Ki-67
expression level.19 In our five cases, both cases with t(8;14)
(q24.1;q32) demonstrated a low Ki-67 (<30%), and following
treatment, one patient (case 4) remained disease free at a 2-year
follow-up, while another patient (case 5) went 16 months
before his disease recurred. Two of our three patients with
increased MYC signal showed high Ki-67 activity (70% to
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Flatley et al / MYC in B-Cell Prolymphocytic Leukemia
>90%) and had an aggressive course, with one patient (case 1)
dying 1 month following diagnosis and another patient (case 2)
surviving only 26 months. Follow-up could not be obtained on
the third patient (case 3).
The treatment approach in CLL has been based on the
status of TP53 abnormalities. Published data have shown
that the use of fludarabine, cyclophosphamide, and rituximab
in patients without TP53 abnormalities induced complete
remissions that held for greater than 5 years but not in the
patients with the TP53 mutation.20 Patients with abnormal
TP53 need to receive alemtuzumab in addition to standard
chemotherapy, because TP53-positive tumors have been
shown to have primary resistance to purine analogue-based
therapy. Currently, the treatment approach for B-PLL is
similar to that of CLL, despite differences in the underlying
biology of the two diseases; resistance to therapy is common in
B-PLL.21 MYC abnormalities may contribute to the aggressive
course of B-PLL in certain patients. Accordingly, identifying
MYC abnormalities may allow for the development of altered
therapeutic regimens for this subset of patients.
Address reprint requests to Dr Fan: Dept of Pathology, Oregon
Health & Science University, 3181 SW Sam Jackson Park Rd,
Mail Code L471, Portland, OR; fang@ohsu.edu.
  This work was supported by the intramural research program,
Department of Pathology, Oregon Health and Science University,
Portland, Oregon, and the intramural research program of
the Center for Cancer Research, National Cancer Institute,
Bethesda, Maryland.
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