When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms.

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.

Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome: A case report and review of literature.

BACKGROUND: Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution. In approximately 10%-15% of patients with severe aplastic anemia (SAA), the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy. In some of these patients, myeloid neoplasms appear during or shortly after immunosuppressive therapy. Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported. CASE SUMMARY: A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria (PNH). With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings in cytological, immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for "SAA." Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches. Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment, and complete hematological remission was achieved within 4 mo of treatment. Frustratingly, the hematological response lasted for only 3 mo, and pancytopenia reemerged. At this time, cytological findings (increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0% of all nucleated hematopoietic cells), immunological findings (increased percentage of cluster of differentiation 34+ cells that accounted for 12.28% of all nucleated hematopoietic cells) and molecular biological findings (identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes) revealed that "SAA" had transformed into acute myeloid leukemia with mutated nucleophosmin-1. The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages, as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo. Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis, and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis. The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism. CONCLUSION: Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature.

BACKGROUND: Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS. CASE SUMMARY: A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode. CONCLUSION: Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.

Flared inflammatory episode transforms advanced myelodysplastic syndrome into aplastic pancytopenia: A case report and literature review.

BACKGROUND: Myelodysplastic syndrome (MDS) is a hematological neoplasm, and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS. Low-risk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia (AA), whereas advanced MDS is characterized by a phenotype of immune exhaustion. MDS can be normo/hyperplastic or hypoplastic. Generally, bone marrow cellularity and myeloblasts increase with disease progression. Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported. CASE SUMMARY: A middle-aged Chinese woman had a 4-year history of leukocytopenia. Six months prior to admission, the patient developed gradually worsening fatigue and performance status. The leukocytopenia further progressed. She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears, an increased percentage of cluster of differentiation (CD)34+CD33+ progenitors in immunotyping analysis, a normal karyotype in cytogenetic analysis, and the identification of somatic mutations in CBL, KMT2D and NF1 in molecular analysis. Initially, neutropenia was the predominant hematological abnormality, with mild anemia and thrombocytosis, and the degree of fatigue was far more severe than the degree of anemia. In the following months, the patient experienced several febrile episodes. Intravenous antibiotic treatments were able to control the febrile episodes, but the elevated inflammatory indices persisted. The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes. With recurrent flares of the inflammatory condition, agranulocytosis and severe anemia developed, with mild thrombocytopenia. During the patient's hospitalization, computed tomography (CT) scans revealed the presence of extensive inflammatory lesions involving the lungs, mediastinum, pleura, gastrointestinal tract, peritoneum and urinary tract, with imaging features suggestive of the reactivation of disseminated tuberculosis. Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic, and the leukemic cells regressed, suggesting that both normal and leukemic hematopoiesis had been heavily suppressed. Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+ cells and an immunological signature resembling that of severe AA (SAA), confirming the regression of the leukemic cells by autoimmune-mediated attacks. The patient demonstrated resistance to multiple drugs, including antituberculotics, recombinant human granulocyte colony-stimulating factor, broad-spectrum antibiotics, voriconazole, ganciclovir, immune suppressants, eltrombopag and intravenous immunoglobulin, which further worsened the hematological injury and patient's performance status. The patient eventually died of overwhelming infection and multidrug resistance. CONCLUSION: Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.

Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria: A case report and review of literature.

BACKGROUND: Thrombotic microangiopathy (TMA) is a group of disorders that converge on excessive platelet aggregation in the microvasculature, leading to consumptive thrombocytopenia, microangiopathic hemolysis and ischemic end-organ dysfunction. In predisposed patients, TMA can be triggered by many environmental factors. Glucocorticoids (GCs) can compromise the vascular endothelium. However, GC-associated TMA has rarely been reported, which may be due to the lack of awareness of clinicians. Given the high frequency of thrombocytopenia during GC treatment, particular attention should be given to this potentially fatal complication. CASE SUMMARY: An elderly Chinese man had a 12-year history of aplastic anemia (AA) and a 3-year history of paroxysmal nocturnal hemoglobinuria (PNH). Three months earlier, methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis. Following GC treatment, his platelet counts and hemoglobin levels rapidly decreased. After admission to our hospital, the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect. However, increasing the GC dose did not alleviate hemolysis, and his cytopenia worsened. Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia. Cluster of differentiation (CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes. In the following days, platelet transfusion was required due to severe thrombocytopenia. Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins. We examined blood smears and found a small number of schistocytes, dacryocytes, acanthocytes and target cells. Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels. The patient's platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation. CONCLUSION: GCs can drive TMA episodes. When thrombocytopenia occurs during GC treatment, TMA should be considered, and GCs should be discontinued.

Bowel inflammatory presentations on computed tomography in adult patients with severe aplastic anemia during flared inflammatory episodes.

BACKGROUND: Patients with severe aplastic anemia (SAA) frequently present with inflammatory episodes, and during flared inflammatory episodes, hematopoietic function is further exacerbated. The gastrointestinal tract is the most common site for infectious and inflammatory diseases, and its structural and functional features confer on it the most potent capacity to affect hematopoietic and immune functions. Computed tomography (CT) is a readily accessible approach to provide highly useful information in detecting morphological changes and guiding further work-ups. AIM: To explore CT imaging presentations of gut inflammatory damage in adult SAA patients during inflammatory episodes. METHODS: We retrospectively evaluated the abdominal CT imaging presentations of 17 hospitalized adult patients with SAA in search of the inflammatory niche when they presented with systemic inflammatory stress and exacerbated hematopoietic function. In this descriptive manuscript, the characteristic images that suggested the presence of gastrointestinal inflammatory damage and related imaging presentations of individual patients were enumerated, analyzed and described. RESULTS: All eligible patients with SAA had CT imaging abnormalities that suggested the presence of an impaired intestinal barrier and increased epithelial permeability. The inflammatory damages were concurrently present in the small intestine, the ileocecal region and the large intestines. Some readily identified imaging signs, such as bowel wall thickening with mural stratification ("water holo sign", "fat holo sign", intramural gas and subserosal pneumatosis) and mesenteric fat proliferation (fat stranding and "creeping fat sign"), fibrotic bowel wall thickening, "balloon sign", rugged colonic configuration, heterogeneity in the bowel wall texture, and adhered and clustered small bowel loop (including various patterns of "abdominal cocoon"), occurred at a high incidence, which suggested that the damaged gastrointestinal tract is a common inflammatory niche responsible for the systemic inflammatory stresses and the exacerbated hematopoietic failure in patients with SAA. Particularly, the "fat holo sign" was present in 7 patients, a rugged colonic configuration was present in 10 patients, the adhesive bowel loop was present in 15 patients, and extraintestinal manifestations suggestive of tuberculosis infections were present in 5 patients. According to the imaging features, a suggestive diagnosis of Crohn's disease was made in 5 patients, ulcerative colitis in 1 patient, chronic periappendiceal abscess in 1 patient, and tuberculosis infection in 5 patients. Other patients were diagnosed with chronic enteroclolitis with acutely aggravated inflammatory damage. CONCLUSION: Patients with SAA had CT imaging patterns that suggested the presence of active chronic inflammatory conditions and aggravated inflammatory damage during flared inflammatory episodes.

Antibiotic and glucocorticoid-induced recapitulated hematological remission in acute myeloid leukemia: A case report and review of literature.

BACKGROUND: Leukemic hematopoietic cells acquire enhanced self-renewal capacity and impaired differentiation. The emergence of symptomatic leukemia also requires the acquisition of a clonal proliferative advantage. Untreated leukemia patients usually experience an aggressive process. However, spontaneous remission occasionally occurs in patients with acute myeloid leukemia (AML), most frequently after recovery from a febrile episode, and this is generally attributed to the triggering of antineoplastic immunity. There may be another explanation for the spontaneous remission as implicated in this paper. CASE SUMMARY: A 63-year-old Chinese man presented with high fever, abdominal pain and urticaria-like skin lesions. He was diagnosed with AML-M4 with t(8;21) (q22;q22)/RUNX1-RUNX1T1 based on morphological, immunological, cytogenetic and molecular analyses. He had a complex chromosome rea-rrangement of 48,XY,t(8;21)(q22;q22),+13,+13[9]/49,idem,+mar[9]/49,idem,+8[2]. He also had a mutated tyrosine kinase domain in fms-like tyrosine kinase 3 gene. He was treated with antibiotics and glucocorticoids for gastrointestinal infection and urticaria-like skin lesions. The infection and skin lesions were quickly resolved. Unexpectedly, he achieved hematological remission along with resolution of the febrile episode, gastrointestinal symptoms and skin lesions. Notably, after relapse, repeating these treatments resulted in a return to hematological remission. Unfortunately, he demonstrated strong resistance to antibiotic and glucocorticoid treatment after the second relapse and died of sepsis from bacterial infection with multidrug resistance. The main clinical feature of this patient was that symptomatic AML emerged with flaring of the gut inflammatory disorder and it subsided after resolution of the inflammation. Learning from the present case raises the possibility that in a subgroup of AML patients, the proliferative advantage of leukemia cells may critically require the presence of inflammatory stresses. CONCLUSION: Inflammatory stresses, most likely arising from gastrointestinal infection, may sustain the growth and survival advantage of leukemic cells.

Acquired aplastic anemia: Is bystander insult to autologous hematopoiesis driven by immune surveillance against malignant cells?

We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations (GCPs). This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments, with each recurrence occurring 7-8 wk from a GCP. After his third recurrence, he was prescribed successive treatment with rifampicin, berberine, and monthly administered GCP for 4 mo, and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy, and eventually died of septic shock. Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis. From the treatment process and laboratory investigations, it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state. Incorporation of rifampicin, berberine, and monthly GCP into cyclosporine can enhance the immunosuppressive effect. In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure, the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.

Severe hyperlipemia-induced pseudoerythrocytosis - Implication for misdiagnosis and blood transfusion: A case report and literature review.

BACKGROUND: Severe hyperlipemia (SHLE) has an impact on the results of many kinds of laboratory tests. Complete blood count (CBC) examination by automated blood cell counter (ABCC) is a quick and convenient measurement for screening abnormalities of blood cells that are triggered by various pathogenic insults in disease diagnosis and for monitoring changes in the treatment of existing hematological conditions. However, CBC results are frequently affected by many intrinsic and extrinsic factors from blood samples, such as in the setting of hypergammaglobulinemia and certain anticoagulants. SHLE could also affect CBC results. CASE SUMMARY: A 33-year-old Chinese male presented with painful foot numbness and abdominal pain. He was initially misdiagnosed as having a myeloproliferative neoplasm (MPN) because of the marked abnormalities in CBC examination by the ABCC. Morphological evaluation of the bone marrow smears and biopsy showed no evidence of MPN. Gene mutations in Breakpoint cluster regions-Abelson murine leukemia viral oncogene homologue 1 (BCR-ABL1), Janus kinase 2 (JAK2), calreticulin (CALR), myeloproliferative leukemia virus (MPL), and colony-stimulating factor 3 receptor (CSF3R) were negative. Having noticed the thick chylomicron layer on blood samples and the dramatically fluctuating CBC results, we speculated that the fat droplets formed by shaking the blood samples in the setting of SHLE were mistakenly identified as blood cells due to the limited parameters of ABCC. Therefore, we removed a large part of the chylomicron layer and then reexamined the CBC, and the CBC results, as we expected, differed significantly from that of the sample before the chylomicron layer was removed. These significant differences had been validated by the subsequently repeated laboratory tests by measuring dual blood samples that the chylomicron layer was removed in one sample and was not in another, and comparing the CBC results. Computerized tomography reexamination of the upper abdomen revealed an exudative lesion surrounding his pancreas. After intensive consultation, definitive diagnosis was made as recurrent pancreatitis, hyperlipemia and pseudoerythrocytosis. CONCLUSION: SHLE may become a potential cause of misdiagnosis of hyperlipemia-related diseases as MPNs and the resultant mistreatment. It may also lead to the misinterpretation of transfusion indications in patients with hematological disorders who critically need blood transfusion for supportive treatment.

Excellent response of severe aplastic anemia to treatment of gut inflammation: A case report and review of the literature.

BACKGROUND: Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia (AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium. CASE SUMMARY: A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However, subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient (namely, psychiatric disorders, hypertension, insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements. CONCLUSION: Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.

[Clinical and laboratory study of a complex translocation t (6; 21; 8) (p22; q22; q22) in two patients with acute myeloid leukemia].

OBJECTIVE: To investigate the clinical and laboratory characteristics of a complex translocation t (6; 21; 8) (p22; q22; q22) in two patients with acute myeloid leukemia. METHODS: Bone marrow (BM) samples were collected at presentation, prepared by short-term (24 hours) unstimulated culture and R-binding, for conventional cytogenetic assay (CCA). The complex translocation was assayed by fluorescence in situ hybridization (FISH) with a dual-color AML1/ETO-specific probe. AML1/ETO chimeric transcript was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In both cases CCA demonstrated a complex translocation, t (6; 8; 21) (p22; q22; q22), which was confirmed by interphase and metaphase FISH and AML1/ETO fusion transcript was detected by RT-PCR. Both the two patients were diagnosed as AML-M(2), but with different immunophenotype and therapeutic outcome. CONCLUSION: The t (6; 21; 8) (p22; q22; q22) is a rare variant of complex translocation of t (8; 21) (q22; q22). More such cases are needed for elucidating its clinical features and prognosis.

[Combination of interphase- and metaphase-fluorescence in situ hybridization to identify 11q23/MLL abnormalities in acute leukemia patients].

OBJECTIVE: To explore a rapid, sensitive and effective method for identifying 11 q23/MLL gene rearrangements and investigate the incidence and clinical features of adult acute leukemia (AL) patients with 11 q23/MLL abnormalities. METHODS: Bone marrow samples from 112 adult AL patients were prepared by short-term (24 hours) unstimulated culture, and karyotyped by R-banding. The abnormal signals were screened by interphase- fluorescence in situ hybridization (FISH) with dual-color break-apart 11 q23/MLL-specific probe, and the 11 q23/MLL gene rearrangements were determined by metaphase-FISH. RESULTS: Of the 112 patients,9 (8. 0%) with 11q23/MLL translocations were revealed by FISH, among which only 4 (3. 6% ) was revealed by CCA. Three patients were reported by CCA to have del( 11) ( q23) , while by FISH assay two of them were 11 q23/MLL translocation and one was true deletion of I lq23 telomeric terminus. Furthermore by FISH assay II q23/MLL translocations were identified in one each patient with normal karyotype, with 11 q + and without overt 11 q23 abnormality. Eight patients with MLL gene amplification including polysome, homogenous staining region (hsr) and double minute chromosome (dmin) were also disclosed by FISH. AL patients with 11 q23/MLL abnormalities were frequently diagnosed as pro-B acute lymphoblastic leukemia (pro-B ALL) ,acute monocytic leukemia (AMoL) or biphenotypic acute leukemia (BAL). CONCLUSION: FISH with dual-color break-apart I q23/MLL -specific probe is a rapid and sensitive method to detect 11 q23/MLL abnormalities, as compared with CCA. FISH also effectively discloses translocations and amplifications involving 11 q23/MLL,and should be performed in patients diagnosed as pro-B ALL,AMoL or BAL, with CCA normal karyotype.