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Expression of JL1 is an effective adjunctive marker of leukemia cutis.

Accurate and specific diagnosis of leukemia cutis (LC) is crucial because such patients experience more aggressive disease progression and require immediate local and systemic treatment. (1-4) Leukemia cutis is strongly associated with extramedullary leukemia and relapse in the bone marrow. (3) Treatment of LC typically involves combination therapy comprising local treatments (eg, radiation therapy or electron beam radiation) and systemic chemotherapy. (5) Histologic diagnosis of LC is fairly straightforward in cases of diffuse tumor cell infiltration, despite variable clinical and histopathologic features. (6,7) However, because the incidence of nonleukemic dermatoses in leukemia patients is significantly higher than that of LC, it is difficult to make a specific diagnosis of LC when only a few leukemic infiltrates are present or leukemic cells display little atypism. (1,8,9) Immunohistochemical markers are helpful in distinguishing leukemia cells from benign inflammatory cells of nonleukemic dermatosis in these situations. Therefore, immunohistochemical markers that are easy to interpret and that can effectively discriminate leukemic cells in routine paraffin-embedded, formalin-fixed tissue should significantly aid in the diagnosis of LC with scant infiltrates.

JL1 is a novel leukemia-associated surface glycoprotein that was initially described in immature double-positive (ie, [CD4.sup.+] [CD8.sup.+]) T cells in the human thymic cortex. (10) JL1 has been subsequently detected in a few subpopulations of bone marrow hematopoietic precursor cells (11) but not in any other healthy human tissue. (12) JL1 is also expressed in acute T-cell lymphoblastic leukemia cells, which are malignant counterparts of immature thymocytes. Interestingly, JL1 has been detected in other acute lymphoid and myeloid leukemias, regardless of their lineages. (12,13) In view of its specific expression in leukemic cells, JL1 can potentially serve as an effective marker of leukemia with promising therapeutic potential. (13,14) Although limited information is available on the biological functions of JL1, previous studies demonstrate that anti-JL1 antibodies induce homotypic aggregation of thymocytes (15) and play an important role in the positive selection of thymocytes. (12,15)

If JL1 were expressed exclusively on leukemic cells of LC, but not on any other skin lesions, it would be a good adjunctive diagnostic marker for LC with scant infiltrates. We assessed JL1 expression patterns via immunohistochemical staining on formalin fixed, paraffin-embedded human skin biopsy specimens from 32 patients diagnosed with LC. To establish whether JL1 expression is specific for leukemic cells, we assessed immunoreactivity in other skin lesions, including those obtained from patients with Sweet syndrome, graft-versus-host disease (GVHD), cutaneous neoplasms, and other inflammatory conditions.

MATERIALS AND METHODS

Patients and Tissue Specimens

All specimens originated from skin biopsies obtained between 1995 and 2007 at the Asan Medical Center and the Samsung Medical Center in Seoul, Korea. Thirty-two cases of LC (Table 1) and 96 nonleukemic cutaneous lesions were collected retrospectively from the surgical pathology files maintained by these institutions (Table 2). This study adhered to the guidelines established by the Declaration of Helsinki and was approved by the institutional review board of Asan Medical Center (2007-01696).

We examined specimens from 32 patients with LC, including 11 acute lymphoblastic leukemia/lymphoma (ALL) and 21 acute myeloid leukemia (AML) cases. The diagnosis of LC was made according to the histologic and immunohistochemical findings of the skin lesions and the patient's bone marrow biopsy results. All patients had prior bone marrow biopsy confirmation with exception of one patient with T-cell ALL (case 8 in Table 3), which was prostate primary. Immunohistochemical staining for either terminal deoxynucleotidyl transferase (TdT) or CD99 was done when the patient had AML, and myeloperoxidase (MPO) was stained if the patient had ALL. In some cases, when the atypical cellular infiltration was obvious on routine histology, no further immunohistochemical staining was performed. Two patients with ALL (cases 6 and 11 in Table 3) had follow-up skin biopsies, which were also LC. In addition, we examined samples from 96 patients with non-LC cutaneous lesions, including 9 cases of Sweet syndrome, 11 cases of GVHD, 66 cases of mass-forming lesions (cutaneous lymphomas [48 of 66], Merkel cell carcinomas [10 of 66], and histiocytic tumors [8 of 66]), and 10 inflammatory lesions. Paraffin-embedded, human, thymic and tonsillar tissues (positive and negative controls, respectively) were obtained from the Asan Medical Center surgical files.

Immunohistochemical Staining

DakoCytomation EnVision+ system-HRP (Dako, Carpinteria, California) was employed for all immunohistochemical staining experiments. Tissue sections 4 mm in thickness were heated, deparaffinized, and rehydrated. Endogenous peroxidase was inactivated, and the antigen retrieval was done by steaming samples in 0.1 mol/L of citrate buffer (pH 6.0) for 60 minutes. After blocking nonspecific binding and washing, slides were incubated at room temperature for 30 minutes with either 1 [micro]g/L murine anti-JL1 monoclonal antibody (kindly provided by Professor Seong Hoe Park, (10-13) MD, PhD) or other primary antibodies: rabbit polyclonal anti-TdT (1:25), rabbit polyclonal anti-human MPO (1:2500), mouse monoclonal anti-human CD43 (1:100), mouse monoclonal anti-human CD99 (1:50), rabbit polyclonal anti-human CD117 (1:400) antibodies (all from Dako, Glostrup, Denmark), and mouse monoclonal anti-human CD34 antibody (1:500, ImmunoTech, Marseille, France). Sections were washed, incubated with peroxidase-labeled polymer for 30 minutes, and visualized by incubation with 3,3-diaminobenzidine and chromogen. Next, sections were counterstained with hematoxylin. Isotype-matched mouse immunoglobulin (Jackson Immunoresearch Laboratories, West Grove, Pennsylvania) was included in all immunohistochemical staining experiments as a negative control, and human thymic tissue was used as a positive control.

Interpretation and Scoring Immunohistochemical Staining

Only nuclear staining was considered positive for TdT and only cytoplasmic staining for MPO. A strong cytoplasmic membrane staining pattern was considered positive for anti JL1, CD34, CD43, CD99, and CD117. The proportion of positive tumor (leukemic) cells of each antibody was scored as follows: 0, if none of the tumor cells were positive; 1, if less than one-tenth of the tumor cells were positive; 2, if one-tenth to less than one-third of the tumor cells were positive; 3, if one-third to less than two-thirds of the tumor cells were positive; 4, if more than two-thirds of the tumor cells were positive. Immunohistochemical staining results were independently scored by 3 pathologists (Y.S.P., S.H.P., and C.S.P.). If there was a discrepancy on the staining score, the case was reviewed, and consensus was reached through discussion.

RESULTS

Expression of JL1 in Leukemic Cells of LC

Among the 32 patients diagnosed with LC, 14 (44%) harbored [JL1.sup.+] cells with distinct membranous expression pattern. The [JL1.sup.+] cases included 7 of the 11 patients (63.6%) with ALL-LC (Table 3) and 7 of the 21 patients (33.3%) with AML-LC (Table 4). Typical cases of ALL-LC or AML-LC showed diffuse infiltration of atypical tumor cells in the dermis with scanty cytoplasm (Figure 1, A and C). The staining score of JL1 in all of the [JL1.sup.+] cases was 4 because more than 90% of these tumors cells were positive (Figure 1, B and D; Table 3 for ALL-LC; Table 4 for AML-LC). The staining patterns and intensities of these cells were equivalent to those of cortical thymocytes in positive controls (Figure 1, E).

We compared the sensitivity as well as the staining scores of JL1 with other commonly used markers for ALL, such as TdT, CD99, CD34, CD117, and CD43 (Table 3). In B-cell ALL-LC, the sensitivity of JL1 was 75% (3 of 4), TdT was 50% (2 of 4), CD99 was 100% (4 of 4), CD34 was 50% (2 of 4), CD117 was 0% (0 of 4), and CD43 was 100% (4 of 4). Although CD99 and CD43 were the most sensitive markers, the specificity was low because reactive lymphoid cells were also positive for these antibodies. JL1 showed the highest sensitivity, except CD99 and CD43. In T-cell ALL-LC, the sensitivity of JL1 was 57.1% (4 of 7), TdT was 85.7% (6 of 7), CD99 was 100% (4 of 4), CD34 was 85.7% (6 of 7), CD117 was 42.8% (3 of 7), and CD43 was 100% (7 of 7). The sensitivity of TdT and CD34 was higher than JL1, but the staining score of JL1 was either 0 or 4, whereas the scores of other markers were variable (Figure 1, B; Table 3).

The World Health Organization classification of the 8 [JL1.sup.+] AML-LC cases were as follows: 2 cases of acute promyelocytic leukemia (AML with t(15;17)(q22;q12) PML/RARA and variants); 1 case of AML, with band 11q23 (MLL) abnormalities; 1 case of AML, minimally differentiated; 2 cases of AML, without maturation; 1 case of acute myelomonocytic leukemia; 1 case of acute erythroid leukemia; and 1 case of biphenotypic acute leukemia (Table 4). We also compared the sensitivity and staining scores of JL1 and other markers (MPO, CD34, CD117, and CD43) in AML-LC. The sensitivity of JL1 in AML-LC was 38% (8 of 21), MPO was 42.9% (9 of 21), CD34 was 90.5% (19 of 21), CD117 was 81% (17 of 21), and CD43 was 100% (21 of 21). CD43 showed highest sensitivity as in ALL-LC, but its specificity was low. Although JL1 showed the lowest sensitivity, the staining score was either 0 or 4 as in ALL-LC, whereas other markers had variable scores (Figure 1, D; Table 4).

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Expression of JL1 With Scant Infiltrates

When JL1 was positive, the staining score of JL1 was invariably high. Therefore, we observed the staining pattern JL1 in cases of scarce infiltrates because a marker that specifically stains most of the tumor cells would be useful in these cases. We examined anti-JL1 and anti-TdT immunohistochemical staining in 2 cases of B-cell ALL-LC (cases 2 and 3; Table 3) with scanty dermal infiltration in which a few atypical cells were infiltrated in the perivascular and periadnexal area (Figure 2, A). JL1 was positive in more than 90% of atypical tumor cells (score, 4; Figure 2, B). Terminal deoxynucleotidyl transferase was also positive, but the proportion of [TdT.sup.+] cells was less than 30% (score, 2; Figure 2, B, inset).

Expression Pattern of JL1 on Follow-up Biopsies

A marker that is stably expressed in leukemic cells after treatment would be of great help during the evaluation of follow-up biopsies in LC because exclusion of more frequent inflammatory skin lesions is essential. Accordingly, we investigated the stability of JL1 expression, as well as other markers. Two patients underwent additional skin biopsies after 11 and 3 months, respectively (cases 5 and 11; Table 3). JL1 maintained its expression in both sets of initial and follow-up biopsies, with similar intensity and proportion (score, 4; Figure 3, A through D). One patient (case 5) maintained expression of all other markers, but the other patient (case 11) lost the expression of TdT and CD34 (Table 3).

[FIGURE 3 OMITTED]

Expression of JL1 in Other Cutaneous Lesions

Treatment for acute leukemia, regardless of whether a patient undergoes bone marrow transplantation, frequently induces the formation of Sweet syndromelike lesions because of toxicity or allergy to chemotherapy. In specific situations, GVHD elicits atypical features similar to those caused by LC. Cutaneous neoplasms, including mycosis fungoides and Merkel cell carcinoma, can also be confused with LC. To confirm the efficacy of JL1 expression in the differential diagnosis of LC, we performed immunohistochemical staining of other skin lesions, including those from patients with Sweet syndrome, GVHD, cutaneous lymphomas, Merkel cell carcinoma, Langerhans cell histiocytosis, eruptive xanthoma, and other inflammatory diseases. None of the cells in these skin lesions expressed JL1 (Figure 4, A through F). Moreover, healthy skin cells, including epidermal, neural, Langerhans cells, melanocytes, hair follicles with adjacent structures, and sweat glands, were negative for JLI (data not shown).

COMMENT

Leukemia cutis manifests as cutaneous eruptions, which result from infiltration of leukemic cells into the skin. (16) However, nonleukemic dermatoses (cutaneous eruptions other than those caused by LC) are more frequently encountered during the clinical course of acute leukemia. These cutaneous eruptions result from adverse drug reactions, skin infections, and inflammatory dermatoses, such as Sweet syndrome. In patients undergoing bone marrow transplantation, cutaneous manifestations of GVHD can also mimic LC. (6,9,17-19) Nonleukemic dermatosis and GVHD often do not require further treatment, apart from conservative management or immunosuppression, and nonleukemic dermatoses (but not GVHD) are usually self-limited. Thus, it is essential to determine whether leukemic cells are present in skin lesions, which would indicate that the patient is in relapse or not in complete remission.

Several markers of leukemic cells are commonly employed, including TdT, MPO, lysozyme, CD10, CD34, CD99, and CD117. Unfortunately, because some of these markers also yield positive results in normal hematopoietic cells, it is sometimes difficult to distinguish leukemic cells from other inflammatory hematopoietic cells. Because of these limitations, staining serial sections with multiple markers and frequently in panels is usually required to confirm the leukemic nature of infiltrated tumor cells. However, there is always a risk of losing tumor cells during multiple serial sections, particularly when infiltrated leukemic cells are scarce. Hence, a more specific marker with strong immunoreactivity should significantly aid in the diagnosis of LC.

The JL1 was originally identified as a novel antigen expressed in double-positive (ie, [CD4.sup.+][CD8.sup.+]) human cortical thymocytes. (10) Subsequently, JL1 was detected in [CD34.sup.+][CD10.sup.+] lymphoid precursors and in some immature myeloid cells in the bone marrow. (11) Although JL1 expression is restricted to a certain population of thymocytes and bone marrow cells, JL1 is expressed in most acute leukemias, regardless of lineage. (12,13) JL1 is thus suggested as an excellent tool for the diagnosis and treatment of leukemia. (12-14)

In this study, JL1 was expressed in 63.6% of ALL-LC cases, 33.3% of AML-LC cases, and in 48.8% of all patients with LC (Table 3). These results are generally consistent with earlier reports, although the positivity rate of JL1 in our study was lower than that reported by previous investigators (specifically, JL1 expression was found in 85.7% of patients with ALL, 69.4% of patients with AML, and 78.4% of all patients with acute leukemia). (12,13) This discrepancy may reflect the differences in sensitivity between immunohistochemistry (used in our study) and flow cytometry (used in previous investigations). However, another previous study using immunohistochemical staining method on paraffin-embedded bone marrow biopsies yielded a higher sensitivity (89%; 16 of 18). (20) Therefore, leukemic cells that infiltrate the skin and those remaining in the blood may be biologically different or [JL1.sup.+] leukemic cells may not transmigrate across dermal vessels to the same extent as [JL1.sup.-] leukemic cells. To confirm this hypothesis, further studies are required to compare the incidence of LC in patients with [JL1.sup.+] and [JL1.sup.-] leukemia.

There were 2 patients who had follow-up biopsies in this study. Samples from these patients remained [JL1.sup.+] during those follow-ups. Although the number of cases is limited for drawing a definitive conclusion, this finding suggests that JL1 expression may not be altered during the course of treatment or time interval between biopsies. More cases should be evaluated in a future study to confirm this persistent expression through disease progression or treatment. A comparison of the clinical features of [JL1.sup.+] and [JL1.sup.-] LC revealed no statistically significant differences in prognoses or treatment responses (data not shown).

Although JL1 did not display higher sensitivity compared with other commonly used markers, JL1 had advantage beyond other markers because JL1 showed invariably high-staining scores when positively stained.

JL1 stained with a strong and distinct cell membrane pattern in more than 90% of tumor cells. This staining pattern of JL1 is simple to interpret because membranous antigen expression is usually easier to analyze than cytoplasmic antigen expression.

The most sensitive markers for both ALL-LC and AML-LC were CD99 and CD43. However, CD99 and CD43 as well as other commonly used markers are known to be positive in reactive hematopoietic cells. TdT (21,22) and CD99 (23) are reliable markers for ALL because they are expressed in leukemic cells of lymphoid lineage. However, [TdT.sup.+] cells are also present in reactive lymph nodes, tonsils, spleens, appendices, and branchial cleft cysts. (24-26) Furthermore, TdT is expressed in patients with other neoplastic conditions, such as Merkel cell carcinoma (27) and some pediatric, nonhematopoietic, small, round-cell solid tumors. (28) CD99 is expressed by several types of malignant neoplasms (such as Ewing sarcoma and synovial sarcoma) and even in healthy tissues (including normal lymphoid cells). (23,28) Myeloperoxidase and lysozyme are markers for leukemic cells of myeloid lineage. (29,30) Although these markers are used to identify myeloid lineage in patients with AML, (6,31) they have rather low specificity for leukemic cells. For example, MPO is expressed during the promyelocyte stage of granulocyte development and in mature, resting granulocytes. (32,33) Thus, healthy myeloid cells (monocytes, macrophages, eosinophils, and mast cells) can contain [MPO.sup.+] cytoplasmic granules. (33,34) CD117, CD10, and CD34 are other useful markers for identifying leukemic cells because they are positive in myeloblasts as well as lymphoblasts. (9) However, these markers are also expressed by other healthy and neoplastic cells in the skin. CD117 is detected in melanocytes and mast cells, (35) CD10 is expressed in reactive skin lesions, (36) and CD34 in endothelial cells. We did not study a large enough number of nonleukemic cases to make a definitive conclusion that JL1 is expressed only in leukemic cells, and there is still the possibility that JL1 may be expressed in other neoplastic or reactive conditions. However, until further information is available, our findings and results from previous studies (12,13) suggest that JL1 expression in skin lesions can be considered as an indicator of the presence of leukemic cells and should aid in the differential diagnosis of LC.

[FIGURE 4 OMITTED]

In summary, we have described the expression profile of JL1 in formalin-fixed, paraffin-embedded biopsy specimens from human skin tissue. Our findings reveal that when positive, JL1 is expressed strongly in most of the leukemic cells in LC, but not in other cutaneous lesions. Although the sensitivity of the anti-JL1 antibody is not sufficiently high for use as a sole marker in the initial diagnosis or screening of LC, its specificity supports its effective application as an adjunctive marker, particularly in patients with low levels of cellular infiltration.

Young Soo Park and So Hyung Park contributed equally to this work. We thank Seong Hoe Park, MD, PhD (Seoul National University, College of Medicine, Seoul, Korea), for generously providing the antibody to JL1, and Shin Kwang Khang, MD, PhD, and Jae Y. Ro, MD, PhD (Asan Medical Center, University of Ulsan College of Medicine, Seoul) for critical comments. This study was supported by a grant W07-408 from the Asan Institute for Life Science, Seoul, and by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST; R13-2008-023-01003).

References

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Young Soo Park, MD, PhD; So Hyung Park, MD; Seo-Jeong Park, MS; Youngji Kim, MS; Kee-Taek Jang, MD, PhD; Young Hyeh Ko, MD, PhD; Mi-Woo Lee, MD, PhD; Joo Ryung Huh, MD, PhD; Chan-Sik Park, MD, PhD

Accepted for publication April 10, 2009.

From the Departments of Pathology (Drs Y. S. Park, S. H. Park, Huh, and C.-S. Park, and Mss S.-J. Park and Kim) and Dermatology (Dr Lee), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;and the Department of Pathology, Samsung Medical Center, Sungkyunkwan University, College of Medicine, Seoul (Drs Jang and Ko).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Chan-Sik Park, MD, PhD, Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea (e-mail: csikpark@ amc.seoul.kr).
Table 1. Number of Cases With Leukemia Cutis

Diagnosis Cases, No.

ALL
 ALL (B) 4
 ALL (T) 7
AML
 ApML, (AML with t[15;17][q22;q12] [PML/
 RARA] and variants) 2
 Acute myeloblastic leukemia, with 11q23 (MLL)
 abnormalities 4
 AML, minimally differentiated 1
 AML, without maturation 4
 Acute myelomonocytic leukemia 6
 Acute monoblastic leukemia 1
 Acute erythroid leukemia 1
 Biphenotypic acute leukemia 2

Abbreviations: ALL, acute lymphoblastic leukemia/lymphoma;ALL (B),
precursor B-lymphoblastic leukemia/lymphoma;ALL (T), precursor
T-lymphoblastic leukemia/lymphoma; AML, acute myeloid leukemia;
ApML, acute promyelocytic leukemia;MLL, myeloid/lymphoid or
mixed-lineage leukemia gene;PML, promyelocytic leukemia gene;
RARA, retinoic acid receptor, alpha gene.

Table 2. Number of Cases With
Nonleukemic Dermatosis

Diagnosis Cases, No.

Sweet syndrome 9
GVHD 11
Mass-forming lesions
 Diffuse large B-cell lymphoma 2
 Marginal zone B-cell lymphoma 1
 Peripheral T-cell lymphoma 17
 NK/T-cell lymphoma 17
 Mycosis fungoides 11
 Merkel cell carcinoma 10
 Langerhans cell histiocytosis 3
 Eruptive xanthoma 5
Inflammatory lesions
 Eosinophilic dermatitis 1
 Mastocytosis 2
 Lichenoid dermatitis 4
 Bullous pemphigoid 2
 Folliculitis 1

Abbreviations: GVHD, graft-versus-host disease; NK, natural killer.

Table 3. Staining Scores of Markers in Leukemia Cutis With Acute
Lymphoblastic Leukemia

 Staining Score
Case No. Age, Diagnosis
 y/Sex JL1 TdT CD99 CD34 CD117 CD43

 1 1/M ALL (B) 4 0 1 2 0 4
 2 2/M ALL (B) 4 2 1 2 0 4
 3 5/M ALL (B) 4 2 3 0 0 4
 4 23/F ALL (B) 0 0 4 0 0 4
 5 22/M ALL (T) 4 3 4 1 0 4
Follow-up 23/M 4 2 4 1 0 4
 6 22/M ALL (T) 4 4 4 4 0 4
 7 24/F ALL (T) 0 4 4 4 0 4
 8 24/M ALL (T) 0 0 1 1 4 2
 9 35/F ALL (T) 0 4 4 3 1 4
 10 38/F ALL (T) 4 4 4 0 1 4
 11 41/M ALL (T) 4 3 4 1 0 1
Follow-up 42/M 4 0 4 0 0 2

Abbreviations: ALL, acute lymphoblastic leukemia/lymphoma; ALL (B),
precursor B/lymphoblastic leukemia/lymphoma; ALL (T), precursor T-
lymphoblastic leukemia/lymphoma; TdT, terminal deoxynucleotidyl
transferase.

Table 4. Staining Scores of Markers in Leukemia Cutis With Acute
Myeloid Leukemia

Case No. Age, y/Sex World Health Organization Diagnosis

12 40/F ApML (AML with t(15;17)(q22;q12) PML/RARA and
 variants)
13 51/M ApML (AML with t(15;17)(q22;q12) PML/RARA and
 variants)
14 15/M Acute myeloblastic leukemia, with 11q23 (MLL)
 abnormalities
15 17/M Acute myeloblastic leukemia, with 11q23 (MLL)
 abnormalities
16 35/F Acute myeloblastic leukemia, with 11q23 (MLL)
 abnormalities
17 45/M Acute myeloblastic leukemia, with 11q23 (MLL)
 abnormalities
18 29/M AML, minimally differentiated
19 25/F AML, without maturation
20 29/F AML, without maturation
21 40/M AML, without maturation
22 65/F AML, without maturation
23 20/M Acute myelomonocytic leukemia
24 35/F Acute myelomonocytic leukemia
25 51/M Acute myelomonocytic leukemia
26 52/F Acute myelomonocytic leukemia
27 54/M Acute myelomonocytic leukemia
28 75/M Acute myelomonocytic leukemia
29 1 d/F Acute monoblastic leukemia
30 58/F Acute erythroid leukemia
31 13/F Biphenotypic acute leukemia
32 20/F Biphenotypic acute leukemia

 Staining Score

Case No. JL1 MPO CD34 CD117 CD43

12 0 4 1 4 4

13 4 0 1 1 3

14 0 0 1 4 4

15 0 0 1 1 4

16 4 0 1 1 4

17 0 0 3 4 4

18 4 0 2 0 4
19 0 4 1 0 3
20 4 4 0 0 4
21 0 2 1 0 2
22 4 0 4 4 4
23 0 3 2 3 4
24 4 0 2 1 4
25 0 0 2 1 3
26 0 0 1 1 4
27 0 0 1 1 4
28 0 3 1 1 1
29 0 3 1 2 4
30 4 0 3 4 4
31 4 4 3 3 4
32 0 1 0 3 4

Abbreviations: AML, acute myeloid leukemia; ApML, acute promyelocytic
leukemia; MLL, myeloid-lymphoid or mixed-lineage leukemia gene; MPO,
myeloperoxidase; PML, promyelocytic leukemia gene; RARA, retinoic acid
receptor, alpha gene.
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Author:Park, Young Soo; Park, So Hyung; Park, Seo-Jeong; Kim, Youngji; Jang, Kee-Taek; Ko, Young Hyeh; Lee,
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Report
Geographic Code:9SOUT
Date:Jan 1, 2010
Words:4896
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